Christos E. Constantinou

Associate Professor of Urology, Emeritus

Bio

Bio

My main recent interest is the application of Biomedical Engineering approaches for the clinical visualization and characterization of the static and dynamic properties of pelvic floor function. This extends to ultrasound Imaging and image processing, construction of computer models and biomechanics analysis of pelvic floor function. It is envisioned that these considerations are important constituents of the clinical evaluation of patients with lower urinary tract dysfunction and urodynamics.

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Research & Scholarship

Current Research and Scholarly Interests

My main recent interest is the application of Biomedical Engineering approaches for the clinical visualization and characterization of the static and dynamic properties of pelvic floor function. This extends to ultrasound Imaging and image processing, construction of computer models and biomechanics analysis of pelvic floor function. It is envisioned that these considerations are important constituents of the clinical evaluation of patients with lower urinary tract dysfunction and urodynamics.

Projects

Dynamics of male pelvic floor function, University of Queensland, Australia

Abstract

At present, existing bladder outlet obstruction (BOO) nomograms for women are still not universally accepted. Moreover, only limited information is available regarding bladder contractility in women. The aim is to present the discussions and recommendations from the think tank session "Can we construct and validate contractility and obstruction nomograms for women?" held at the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK.An overview of clinical significance, bladder mechanics and modelling, lack of existing nomograms for women, and development of new nomograms were presented and discussed in a multidisciplinary think tank session. This think tank session was based on a collaboration between physicians, engineers, and researchers and consensus was achieved on future research initiatives.Based on the think tank discussion, the ICI-RS panel put forward the following recommendations: the need to acquire normative age-matched data in women to define "normal" and "pathological" values of urodynamic parameters; the inclusion of additional clinical data in new nomograms and the use of this extra dimension to develop clinically applicable nomograms for female BOO and contractility; and finally, the need to take into account the variability of BOO in women when developing female bladder contractility nomograms.

When should video and EMG be added to urodynamics in children with lower urinary tract dysfunction and is this justified by the evidence? ICI-RS 2014NEUROUROLOGY AND URODYNAMICSAnding, R., Smith, P., de Jong, T., Constantinou, C., Cardozo, L., Rosier, P.2016; 35 (2): 331-335

Abstract

An ICI-RS Think Tank in 2014 discussed and evaluated the evidence for adding video and EMG to urodynamics (UDS) in children and also highlighted evidence gaps, with the aim of recommending further clinical and research protocols.A systematic analysis of the relevant literature for both X-ray (video) studies and electromyography, in combination with UDS in children with lower urinary tract dysfunction (LUTD), is summarized in this manuscript. The technical aspects are also critically reviewed.The body of evidence for the addition of X-ray (video) to filling and voiding cystometry and the evidence for the addition of pelvic muscle surface electromyography to urodynamics is scanty and insufficient. Standards are poor and variable so uncontrolled expert opinion dominates practice.The Think Tank has recommended that standardized ALARA ("As Low As Reasonably Achievable") principles should be adopted for video-urodynamics in children. The risk-benefit balance of X-ray exposure needs to be better evaluated and defined. Evaluation of images should be standardized and the association with pressure changes better analyzed and reported. Children's pelvic muscle surface electromyography technique should be standardized, technically improved, and its diagnostic relevance should be better evaluated.

Abstract

These guidelines provide benchmarks for the performance of urodynamic equipment, and have been developed by the International Continence Society to assist purchasing decisions, design requirements, and performance checks. The guidelines suggest ranges of specification for uroflowmetry, volume, pressure, and EMG measurement, along with recommendations for user interfaces and performance tests. Factors affecting measurement relating to the different technologies used are also described. Summary tables of essential and desirable features are included for ease of reference. It is emphasized that these guidelines can only contribute to good urodynamics if equipment is used properly, in accordance with good practice.

Abstract

To develop a method to quantify displacement of pelvic structures during contraction of the pelvic floor muscles from transperineal ultrasound images in men and investigate the reliability of the method between days.Ten healthy male volunteers (aged 28-41 years) attended 2 separate data collection sessions. Ultrasound images were recorded during voluntary pelvic floor muscle contractions in cine-loop (video) format with the transducer aligned in the midsagittal plane on the perineum. Five anatomic points were defined to represent contraction from striated urethral sphincter (SUS), levator ani (LA), and bulbocavernosus (BC) muscles. Displacement of each point was calculated between the relaxed and contracted-state images. Intraclass correlation coefficient (ICC) values were calculated from displacement data to assess reliability of the method between days.Displacements of the 5 anatomic points closely matched predictions based on anatomic considerations of the male pelvic musculature. ICC values for displacement data calculated from 1, 2, and 3 repetitions ranged between 0.82 and 0.95 for ICC (2,1), 0.85 and 0.97 for ICC (2,2), and 0.86 and 0.97 for ICC (2,3), respectively.The new method reliably calculates displacements of points previously validated for women (ano-rectal junction and bladder base) in addition to new measures of muscle actions (SUS and BC) specific to men. Future use might include assessment of clinical populations to understand how these displacements relate to symptoms of incontinence.

Abstract

Transperineal ultrasound imaging enables the minimally invasive assessment of pelvic floor muscle function. Although commonly used in women, the approach has rarely been reported in men. This approach has advantages because the midsagittal view visualizes a bony landmark and the entire urethral length. This allows investigation of the displacement of multiple points along the urethra and the unique mechanical actions of multiple muscles that could influence continence. We used a new transperineal ultrasound technique to compare the relative displacement of urethrovesical junction, anorectal junction and distal urethra during voluntary pelvic floor muscle contractions in continent men.We performed measurement and comparison of urethral displacement at specific urethral regions in 10 continent men (age range 28 to 41 years). Measures made on 2-dimensional midsagittal plane ultrasound images included the displacements of specific points along the urethra. Anatomical considerations suggest that these are caused by contraction of the levator ani, striated urethral sphincter and bulbocavernosus muscles. Pearson's correlation coefficient was used to investigate the relationship between displacements of pairs of points.Data show individual variation in displacement of the distal urethra (striated urethral sphincter contraction) and urethrovesical junction (levator ani contraction). A strong inverse linear relationship (0.723) between displacements of these points indicates 2 alternative strategies of urethral movement.Transperineal ultrasound imaging allows the simultaneous investigation of multiple pelvic floor muscles by measuring urethral displacement. The data provide evidence of different but coordinated strategies of urethral displacement in men.

Abstract

The pelvic tissue of women with pelvic organ prolapse is stiffer than that of controls but there are scant data on the collagen composition that corresponds to these mechanical properties. We evaluated human vaginal wall stiffness using the novel scanning haptic microscope and correlated these measurements to collagen expression in women with and without pelvic organ prolapse. In this simultaneous biomechanical and biochemical assessment we evaluated the usefulness of this measurement technology for pelvic floor disorder research and confirmed an association between mechanical properties and composition.The elastic constant (a measure of stiffness) of vaginal wall tissue was measured with the scanning haptic microscope. Protein expression of collagen types I and III of the same tissues were determined by Western blot. The Student t test was used for comparisons between groups.The anterior and posterior vaginal walls of premenopausal and postmenopausal women with pelvic organ prolapse were significantly stiffer than those of controls (p <0.05). Collagen III protein expression in the anterior vaginal wall in the control group was higher than in menopausal women. Collagen I expression was not significantly different between controls and cases.The scanning haptic microscope produced reliable mechanical measurements in small tissue samples without tissue destruction. Vaginal wall tissues are stiffer in women with pelvic organ prolapse than in controls. This vaginal wall stiffness was associated with lower protein expression of collagen III in the vaginal wall compared to that in asymptomatic controls.

Abstract

Visualization of the geometric deformation and associated displacement patterns of tubular abdominal organs to mechanical stimuli provides a quantitative measure that is useful in modeling their elastic properties. The origin of the stimulus may be the result of direct and voluntary muscle contraction or in response to a triggered reflex activity. Using trans-perineal 2D ultrasound imaging we examined the characteristics of deformation and displacement of these organs in response to voluntary activity, contraction, straining, and fast reflex responses to stimuli such as coughing. The relative time sequence in movement was examined by serially segmenting the outline of these structures and mapping their temporal characteristics.

Abstract

Previous studies have demonstrated that the stiffness of cancerous cells reflects their pathological stage and progression rates, with increased cancerous cell stiffness associated with increased aggressiveness. Therefore, the elasticity of the cancerous cells has the potential to be used as an indicator of the cancer's aggressiveness. However, the sensitivity and resolution of current palpation and imaging techniques are not sufficient to detect small cancerous tissues. In previous studies, we developed a tactile-based device to map with high resolution the stiffness of a tissue section. The purpose of this study is to evaluate this device using different tissues (BPH, Cancer and PZ) collected from human prostates. The preliminary results show that the tactile device is sensitive enough to tell the differences of the stiffness of different tissues. The results also disclosed the factors (humidity, temperature and tissue degradation) which could dramatically affect the results of stiffness mapping. The tactile technology described in this paper has the potential to help disclose the underlying mechanical mechanisms that lead to increased stiffness in prostate tumors.

Abstract

We simulated the way that pelvic floor muscles (PFM) generate zonal compression on the vagina and urethra in order to maintain urinary continence. Raw data were obtained using a probe to map the distribution of vaginal closure forces. Simulation model was made using ordinary Spring-mass model. The biomechanical properties are applied to the spring of the model. We simulated four models that are applied to asymptomatic subjects as controls and patients based on information obtained from the measured force maps using a vaginal probe. PFM values are measured when subjects are relaxed and during voluntary PFM contraction. Results show that simulation clearly distinguished between controls and patents and demonstrates that in the controls, after a period of 0.075 sec from the time when the rest force was added, the model was deformed to a neutral shape, and after another period of 0.075 sec from the time when the contract force was added at intervals of 0.001 sec, the closure force reaches maximum. The results render the simulation of the vaginal wall deformations that was obtained directly by the force maps. It shows that in controls the wall model is significantly deformed compared to that from the patient's model. In this research we simulated the response of the vaginal walls using spring mass model and the force maps of vaginal closure forces applied to control subjects and patients. The process of deformation of the vaginal wall is thus visualized demonstrating the relative pathologic differences between the two groups.

Abstract

Current measurement tools have difficulty identifying the automatic physiologic processes maintaining continence, and many questions still remain about pelvic floor muscle (PFM) function during automatic events.To perform a feasibility study to characterise the displacement, velocity, and acceleration of the PFM and the urethra during a cough.A volunteer convenience sample of 23 continent women and 9 women with stress urinary incontinence (SUI) from the general community of San Francisco Bay Area was studied.Methods included perineal ultrasound imaging, motion tracking of the urogenital structures, and digital vaginal examination. Statistical analysis used one-tailed unpaired student t tests, and Welch's correction was applied when variances were unequal.The cough reflex activated the PFM of continent women to compress the urogenital structures towards the pubic symphysis, which was absent in women with SUI. The maximum accelerations that acted on the PFM during a cough were generally more similar than the velocities and displacements. The urethras of women with SUI were exposed to uncontrolled transverse acceleration and were displaced more than twice as far (p=0.0002), with almost twice the velocity (p=0.0015) of the urethras of continent women. Caution regarding the generalisability of this study is warranted due to the small number of women in the SUI group and the significant difference in parity between groups.During a cough, normal PFM function produces timely compression of the pelvic floor and additional external support to the urethra, reducing displacement, velocity, and acceleration. In women with SUI, who have weaker urethral attachments, this shortening contraction does not occur; consequently, the urethras of women with SUI move further and faster for a longer duration.

Abstract

In this review the diagnostic potential of evaluating female pelvic floor muscle (PFM) function using magnetic and ultrasound imaging in the context of urodynamic observations is considered in terms of determining the mechanisms of urinary continence. A new approach is used to consider the dynamics of PFM activity by introducing new parameters derived from imaging. Novel image-processing techniques are applied to illustrate the static anatomy and dynamics of PFM function of stress incontinent women pre- and post-operatively as compared to asymptomatic subjects. Function was evaluated from the dynamics of organ displacement produced during voluntary and reflex activation. Technical innovations include the use of ultrasound analysis for movement of structures during maneuvers that are associated with external stimuli. Enabling this approach is the development of criteria and fresh and unique parameters that define the kinematics of PFM function. Principal among these parameters, are displacement, velocity, acceleration and the trajectory of pelvic floor landmarks. To accomplish this objective, movement detection, including motion tracking algorithms and segmentation algorithms were developed to derive new parameters of trajectory, displacement, velocity and acceleration, and strain of pelvic structures during different maneuvers. Results highlight the importance of timing the movement and deformation to fast and stressful maneuvers, which are important for understanding the neuromuscular control and function of PFM. Furthermore, observations suggest that timing of responses is a significant factor separating the continent from the incontinent subjects.

Abstract

Tactile sensors in general are used for measuring the physical parameters associated with contact between sensor and object. Tactile resonance sensors in particular are based on the principle of measuring the frequency shift, Deltaf, defined as the difference between a freely vibrating sensor resonance frequency and the resonance frequency measured when the sensor makes contact to an object. Deltaf is therefore related to the acoustic impedance of the object and can be used to characterize its material properties. In medicine, tactile resonance sensor systems have been developed for the detection of cancer, human ovum fertility, eye pressure and oedema. In 1992 a Japanese research group published a paper presenting a unique phase shift circuit to facilitate resonance measurements. In this review we summarize the current state-of-the-art of tactile resonance sensors in medicine based on the phase shift circuit and discuss the relevance of the measured parameters for clinical diagnosis. Future trends and applications enabled by this technology are also predicted.

Abstract

We characterized the vaginal pressure profile as a representation of closure forces along the length and circumference of the vaginal wall. Vaginal pressure profile data were used to test the hypothesis that the strength of pelvic floor muscle contractions differs significantly between continent women and women with stress urinary incontinence.Vaginal pressure profile recordings were made in 23 continent subjects and in 10 patients with stress urinary incontinence. The recordings characterized closure forces along the entire length of the vagina and identified differences among the anterior, posterior, left and right sides of the vaginal wall. Using a novel, directionally sensitive vaginal probe we made vaginal pressure profile measurements with the women at rest and during pelvic floor muscle contraction while supine.The nature of the vaginal pressure profile was characterized in terms of force distribution in the anterior and posterior vaginal walls, which was significantly greater than that on the left and right sides. The continent group had significant greater maximum pressure than the stress urinary incontinence group on the posterior side at rest (mean +/- SE 3.4 +/- 0.3 vs 2.01 +/- 0.36 N/cm(2)) and during pelvic floor muscle contraction (4.18 +/- 0.26 vs 2.25 +/- 0.41 N/cm(2)). The activity pressure difference between the posterior and anterior vaginal walls in the continent group was significantly increased when the pelvic floor muscles contracted vs that at rest (3.29 +/- 0.21 vs 2.45 +/- 0.26 N/cm(2)). However, the change observed in the stress urinary incontinence group was not significant (1.85 +/- 0.38 vs 1.35 +/- 0.27 N/cm(2)).The results demonstrate that the voluntary pelvic floor muscles impose significant closure forces along the vaginal wall of continent women but not in women with stress urinary incontinence. The implication of these findings is that extrinsic urethral closure pressure is insufficiently augmented by pelvic floor muscle contraction in women with stress urinary incontinence.

Abstract

Real time ultrasound imaging is one of the many ways to clinically evaluate the anatomical and functional condition of female pelvic floor in patients with urinary incontinence. Reflex arc testing of the displacement of uro-gynecological structures during imaging provides a non-invasive way of visualizing their motility. The response from such tests invariably contains a very large amount of visual information, which is not readily captured and assimilated by the observer because it occurs so fast. For this reason only a portion of available information is retained, typically the beginning end ending frame of the image is preserved. Using video motion tracking, parameters were identified to define important biomechanical and temporal relationships. We conclude that new and clinically significant amount of original information about the female pelvic floor can be obtained through the proposed analysis of visualizations.

Abstract

Clinically the strength of the contraction of the female pelvic floor is qualitatively evaluated by vaginal tactile palpation. We therefore developed a probe to enable the quantitative evaluation of the closure pressures along the vagina. Four force sensors mounted on the four orthogonal directions of an intra-vaginal probe were used to measure the vaginal pressure profile (VPP) along the vaginal wall. Clinical experiments on 23 controls and 10 patients with stress urinary incontinence (SUI) were performed using the probe to test the hypothesis that the strength of pelvic floor muscle (PFM) contractions, imposed by voluntary contraction, is related to urinary continence. The results show that VPPs, characterized in terms of pressure distribution on the anterior and posterior vaginal walls, are significantly greater than those in the left and right vaginal walls. When the PFM contracted, the positions of the maximum posterior pressures in continent females and SUI patients were 0.63+/-0.15 cm and 1.19+/-0.2 cm proximal from their peak points of anterior pressure, which are 1.52+/-0.09 cm and 1.69+/-0.13 cm proximal from the introitus of vagina, respectively. The statistical analysis shows that the maximum posterior vaginal pressures of the controls were significantly greater than those of the SUI patients both at rest (continent: 3.4+/-0.3 N cm(-2), SUI: 2.01+/-0.36 N cm(-2), p<0.05) and during PFM contraction (continent: 4.18+/-0.26 N cm(-2), SUI: 2.25+/-0.41 N cm(-2), p<0.01). In addition, the difference between the posterior and anterior vaginal walls is significantly increased when the controls contract the PFM. By contrast, there are no significant differences in the SUI group. The results show that the VPP measured by the prototype probe can be used to quantitatively evaluate the strength of the PFM, which is a clinical index for the diagnosis or assessment of female SUI.

Abstract

We quantified the effect of pelvic floor muscle training on the anatomical configuration of the levator ani using magnetic resonance imaging.Five female participants with stress urinary incontinence underwent magnetic resonance imaging before and after participating in a pelvic floor muscle physiotherapy program. Axial T1-weighted images of the levator ani were taken with the participant in a supine position. Source images were then manually segmented and surface modeling was applied to build a 3-dimensional model of the levator ani. Models were then measured to determine the levator ani surface area as well as the encircled volume at rest and during voluntary contraction. The percentage of levator ani retraction and symphysis pubis movement during voluntary contraction before and after physiotherapy were also measured.After physiotherapy the levator ani surface area at rest was significantly smaller than before physiotherapy, decreasing from 677.11 +/- 45.00 to 620.48 +/- 36.14 mm(2) (p = 0.04). The relative reduction in volume encircled by the levator ani during contraction increased significantly from -11.66 +/- 7.42 to -26.02 +/- 13.52 mm(3) (p = 0.04). Levator ani surface retraction during a voluntary contraction increased significantly from 65.61% +/- 17.07% to 81.70% +/- 16.30% (p = 0.02). Symphysis pubis movement during pelvic floor muscle contraction decreased from 1.45 +/- 1.32 to 0.44 +/- 0.61 mm (p = 0.05).Findings from this preliminary study indicate that pelvic floor muscle training results in anatomical changes in the levator ani and reduction of pubic movement. These results provide insight into the possible anatomical mechanisms through which physiotherapy enables the pelvic floor muscle to minimize urine leakage.

Abstract

Ultrasound imaging of the pelvic floor carries diagnostically important information about the dynamic response of the pelvic floor muscles (PFM) to potentially incontinence-producing stress, which cannot be readily captured and assimilated by the observer during the scanning process. We presented an approach based on motion tracking quantitatively to analyze the dynamic parameters of PFM on the ano-rectal angle (ARA). Perineal ultrasonography was performed on 22 asymptomatic females and nine stress urinary incontinent (SUI) patients with a broad age distribution and parity. The ventral-dorsal and cephalad-caudad movements of the ARA were resolved and kinematic parameters, in terms of displacement, trajectory, velocity and acceleration, were analyzed. The results revealed the possible mechanisms of PFM responses to prevent the urine from incontinence in fast and stress events such as coughs. The statistical analyses showed that the PFM responses of the healthy subjects and the SUI patients are significantly different in both the supine and standing experiments.

A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTSNEUROUROLOGY AND URODYNAMICSEdgar, A. D., Levin, R., Constantinou, C. E., Denis, L.2007; 26 (4): 458-463

Abstract

Despite an unremitting increase in the number of patients presenting symptoms of benign prostate hyperplasia (BPH), the viable treatment options remain relatively limited when compared to other disorders of aging. This has spurred an interest in so-called alternative medicines, many of which continue to be used in spite of the more recent emergence of rationally targeted therapies. Nonetheless, in the case of plant extracts, the vast majority of these have not been subjected to the same rigorous pre-clinical pharmacological testing and large-scale clinical trials now required by health authorities. Furthermore, demonstration of their clinical efficacy in BPH has been hindered by trials of limited duration with a high placebo response. Beginning with a preliminary demonstration of in vitro inhibition of growth factor-mediated fibroblast proliferation with Pygeum africanum extract, a detailed series of in vitro and in vivo studies on prostate growth and bladder function were undertaken. These studies, reviewed herein, have permitted the identification of putative molecular targets of Pygeum africanum extract affecting both growth factor-mediated prostate growth as well as specific parameters of bladder function. These results, corroborated in part by short-term clinical efficacy, set the stage for a large-scale clinical trial to investigate the efficacy of Pygeum africanum extract in the treatment of lower urinary tract symptoms.

Abstract

The development of a vaginal probe for the evaluation of the dynamics of pelvic floor function is described. Fundamental criteria in the design of this probe involves the incorporation of a means of assessing whether the isotonic forces closing the vagina are equally distributed or whether they are greater in some directions than others. The aim of this study is to present the design of directionally sensitive multi-sensor probe, having circumferential spatial resolution, constructed to identify the distribution of anisotropic forces acting on the vagina following voluntary and reflex pelvic floor contractions.Probe system consists of four pairs of force/displacement sensors mounted on leaf springs enabling isotonic measurements of voluntary and reflex contractions. Assembly is retractable to 23 mm for insertion, and expandable to 60 mm for measurement. Simultaneous measurements were made of force and displacement with the sensors oriented in the anterior/posterior and left/right orientation of the vagina. Using this probe, measurements were carried out to identify the temporal and spatial characteristic response of the vaginal wall. Data were analyzed with respect to voluntary pelvic floor and cough-induced contractions of nine subjects having a mean age of 64 years.A robust probe system was developed and measurements were successfully made. Initial results show that the maximum force and displacement occurs during reflex contractions in the anterior aspect of the vagina validating the anisotropic nature of the forces acting on the vaginal wall. The data also show that both the force and displacement produced by the cough-induced has a higher magnitude than voluntary pelvic floor contraction.A directional multi-sensor vaginal probe has been developed to evaluate the force and displacement produced during isotonic pelvic floor contractions. Analysis of the results provided new biomechanical data demonstrating the anisotropic nature of vaginal closure as a consequence of pelvic floor contractions.

Evaluation of the dynamic responses of female pelvic floor using a novel vaginal probe5th World Congress of Biomechanics/World Council of BiomechanicsConstantinou, C. E., Omata, S., Yoshimura, Y., Peng, Q.WILEY-BLACKWELL.2007: 297–315

Abstract

The female pelvic floor (PF) provides anatomical support to many visceral organs, such as uterus, bladder, urethra, vagina, and rectum. Physiologically, the PF is made up of a number of highly coordinated muscle groups organized to respond to postural and abdominal stresses to maintain continence. In this article, we describe a new methodology for the evaluation of PF strength using a novel vaginal probe design, having force and displacement sensors. This design was derived on the basis of imaging data showing that force/displacement characteristics are important determinants of the integrity of the PF function. The prototype probe used was constructed to evaluate the dynamic responses to slow voluntary contractions as well as reflex stress contractions. Initial clinical experiments were performed on nine healthy female subjects. The probe recorded the force and displacement signals on the anterior and posterior sides of the subjects' middle vaginal wall in voluntary PF muscle contraction and cough. The time domain and frequency domain characteristics of the dynamic responses, including the force and displacement responses, of the vaginal wall were measured and the power and energy associated with the dynamic responses of the PF were analyzed showing the differences between the dynamic characteristics of the voluntary PF muscle contraction and cough. Results show that voluntary PF muscle contractions have higher amplitudes, longer duration, and higher power than reflex contractions. The design of this probe enables the measurement of force and displacement during rapidly occurring events.

Abstract

What is it that the clinician "feels" during a digital rectal examination? To answer this question, it is necessary to measure the elastic properties of the prostate and verify the stiffness values with histological examination. Therefore, we devised an Elasticity Mapping System to evaluate the elastic properties of various histopathological grades of prostate cancer in relation to benign prostatic hyperplasia (BPH) and normal tissue. The system consists of a micro tactile sensor, a three-axis (XYZ) with one (fine Z) micromanipulation stage, a stereoscope camera and a measurement chamber. Using this methodology we mapped the elasticity of human prostate cancer (CaP) and it was obviously observed that the node was significantly harder than surrounding normal tissues and had some textures.

Abstract

We present the analysis of sequences of voluntarily and reflexly generated pelvic floor muscle (PFM) contractions on the urethra, vagina, and rectum. A succession of observations were taken of perineal ultrasound at a frequency of 3.5 MHz imaging using a curved linear array probe in the sagittal plane and the videos captured and stored. An edge extraction algorithm was used to outline the coordinates of the symphysis pubis, urethra, and rectum interfaces on a frame-by-frame basis for sequences of 10-20 s. During each PFM contraction, the trajectory of the boundary of each structure was evaluated, colour coded, and overlaid to characterize the sequential history of the ensuing movement. The resulting image analysis was focused to reveal the anatomical displacement of the urogenital structures, which enables the evaluation of their biomechanical parameters in terms of displacement, velocity, and acceleration at any point in time. On the basis of these observations, the biomechanical mechanisms of pelvic floor muscle responses to voluntary and reflex contractions can be identified. It is concluded that a considerable amount of new, potentially useful clinical information can be revealed from video recordings of perineal ultrasound using the image analysis approach proposed.

Abstract

An ultrasound-based remote sensing method to evaluate the mechanical properties of materials is presented. This method consists of a disk-shaped, piezoelectric transducer, operating at its resonance frequency, and a phase-shifted, feedback circuit. Mechanical parameters are derived by analyzing the signal contained in the phase-shifted values of the reflected signal. It is concluded that, using this novel transducer system and signal processing, remote mechanical measurements can be made. Such measurements obviate the need to apply the force-deformation approach and may be used to enable stiffness imaging.

Abstract

The incorporation of novel broad band sensory modalities, integrating tactile technology, with visual and auditory signals into the evolution of the next generation of surgical robotic is likely to significantly enhance their utility and safety. In this paper considerations are made of a system, where tactile information together with visual and audio feedback are integrated into a multisensory surgical support platform. The tactile sensor system uses a piezoelectric transducer (PZT) system to evaluate the haptic properties of tissues. The spatial position of the sensor is tracked by a video camera, visualizing the location of the marker. Tactile information is additionally converted to an audio signal, to represent tissue properties in terms of a frequency/amplitude modulated signal. Representative data were obtained from biological tissues demonstrating that the technology developed has potential applications in virtual systems or robotic tele-medical care. In view of these technical developments, consideration is made as to whether visual audio and tactile modalities act as independent sources of information.

Abstract

Four different experiments in animals were performed to evaluate the influence of pyelo-ureteral surgery on the function of the upper urinary tract.Experiment I: In 17 female guinea pigs pyelo-ureteral anastomosis was performed microsurgically. Three months later, the ureteral peristalsis was investigated by measuring the intraureteral pressure and the in vitro activity of the renal pelvic and ureteric wall was analysed. Experiment II: 10 rats were used for microsurgical uretero-ureteral anastomosis. One month after surgery the pyelo-ureteral peristalsis was examined by videomicroscopy while simultaneously measuring the renal pelvic and intravesical pressure. Subsequently the kidneys were removed for histological examination. Experiment III: In 2 pigs unilateral pyeloplasty was performed. Using an implanted transmitter the intravesical and the renal pelvic pressures were recorded continuously over a time interval of 3 months. Five months after surgery the pyelo-ureteral peristalsis was investigated by pyelography. The kidneys were then removed for histological and biomechanical examinations. Experiment IV: A partial artificial obstruction was performed in 16 guinea pigs by implanting the ureter into the psoas muscle. Two to six months following surgery their upper urinary tracts were removed for analysis of in vitro activity as well as histological and immunohistochemical investigations of the ureter and renal pelvis.Experiment I: Ultrasound investigation showed in all cases a significant dilation of the renal pelvis. The ureteral contraction frequency distally was decreased in vivo as well as in vitro (p <0.05) compared with the controls. Experiment II: Videomicroscopic imaging showed in eight out of nine cases an interruption of the peristaltic wave below the anastomosis; the ureteral peristalsis was restored distally by ureteral contractions with a decreased frequency. Retroperistalsis was seen in the lower part of the ureter. The frequency of renal pelvic and ureteral contractions were decreased (p <0.05). Renal pelvic baseline pressure as well as contraction amplitude were irregularly changed. Histological examinations showed increased connective tissue within the renal pelvic wall in all cases. Experiment III: In both pigs an intermittent change in contraction frequency of the renal pelvis was found, associated with a changing contraction amplitude. Five months after surgery an interruption of the peristaltic wave was detected in both pigs. Histological examinations showed increased connective tissue within the renal pelvic wall. The stiffness of caliceal and pelvic tissue was lower following the pyeloplasty compared to the controls. Experiment IV: Following artificial partial ureteral obstruction in all guinea pigs the in vitro investigations showed an increased spontaneous activity of the upper urinary tract except in the proximal part of the ureter. Ureteral obstruction produced a change in contraction pattern of the proximal ureter and a decrease in contraction frequency of the distal ureter. Immunohistochemical investigations revealed rarefication and disorientation of nerve fibres within the proximal ureteric wall.Surgical interruption of the ureteral continuity and re-anastomosis cause a temporary disruption of the peristaltic wave at the anastomosis site. Ureteral peristalsis is restored by ureteral contractions associated with retroperistalsis as well as a decreased contraction frequency. Uretero-ureteral anastomosis in rats, pyelo-ureteral anastomosis in guinea pigs and pyeloplasty in pigs seem to influence the upper urinary tract similarly to a chronical functional obstruction, causing changes in pyelo-ureteral motility and spontaneous muscular activity of the renal pelvic and ureteral wall as well as biomechanical and histological characteristics.

Abstract

Benign prostatic hypertrophy (BPH) produces a variety of changes in the urodynamic pattern of micturition and is usually associated with high detrusor voiding pressure and poor urine flow-rate. In most previous experimental models, designed to simulate this condition, some degree of obstruction is immediately imposed by the technique employed to produce urethral occlusion. Consequently these models cannot reproduce the gradual onset of obstruction. In the present study a canine prostatic enlargement model, using 5alpha-dihydrotestosterone (DHT) + 17beta-estradiol (E) was adapted in order to produce a more gradual onset of partial obstruction and impaired voiding.Hormonally induced prostatic enlargement was produced using seven beagles, given DHT 75 mg/day together with E 0.75 mg/day for 28 days via an implantable pump. The functional effects of DHT + E treatment on micturition pressure/flow were measured in the conscious animal. Identical measurements were also made using a separate older group of five beagles with symptoms of BPH. In addition seven beagles similarly instrumented were used as controls.Pressure/flow studies show that DHT + E produced obstructive micturition, characterized by a significantly increased micturition detrusor pressure, from 33.3 +/- 10.5 to 50.8 +/- 10.7 cmH(2)O and significantly decreased low urine flow-rate from 8.6 +/- 2.1 to 6.9 +/- 0.9 ml/sec. Associated with the obstructive micturition, this treatment increased wet prostate weight from 11.9 +/- 2.5 to 31.6 +/- 10.0 g. Prostate volume of the BPH beagles was 29.3 +/- 8.9 g. Morphologic studies show that DHT + E produced epithelial hyperplasia extending focally into the lumen.Hormonally induced prostate growth produced bladder obstruction, in terms of pressure/flow characteristics, that are analogous to BPH. It is suggested that this type of hormonal treatment can be used to create a model for the study of the effects of controlled increased in prostate growth and the development of BPH on micturition.

Abstract

Surgical practice would be significantly enhanced with robotic systems incorporating tactile sensors. Current tactile sensor technology consists mainly of strain gauge elements having a limited bandwidth. A novel tactile sensor system, has been developed using a piezoelectric transducer(PZT), to simulate the properties of the human hand for use as a surgical support instrument and a palpation probe. Visualization of tactile information as an audio signal is provided, representing tissue properties in terms of an amplitude and frequency modulated signal. Representative data measured from pig brain, lung, pancreas, tongue and liver show that the changes in frequency corresponds to tissues stiffness and contact pressure. The technology developed in this new surgical support system has potential applications in virtual systems or robotic tele-medical care.

Abstract

Stiffness is an important parameter in determining the physical properties of living tissue. Recently, considerable biomedical attention has centered on the mechanical properties of living tissues at the single cell level. In the present paper, the Young's modulus of zona pellucida of bovine ovum was calculated using Micro Tactile Sensor (MTS) fabricated using piezoelectric (PZT) material. The sensor consists of a needle-shaped 20-microm transduction point made using a micro-electrode puller and mounted on a micro-manipulator platform. Measurements were made under microscopic control, using a suction pipette to support the ovum in the same horizontal axis as the MTS. Young's modulus of ovum was found to be 25.3+/-7.94 kPa (n=28). This value was indirectly determined based on calibration curves relating change in resonance frequency (Deltaf(0)) of the sensor with tip displacement for gelatin at concentrations of 4%, 6%, and 8%. The regression equation between the rate of change in resonance frequency (versus sensor tip displacement), Deltaf(0)/x and Young's modulus is Deltaf(0)/x (Hz/microm)=0.2992 x Young's modulus (kPa)-1.0363. It is concluded that a reason that the stiffness of ovum measured in the present study is approximately six times larger than previously reported, may be due to the absence of large deformation present in of existing methodologies.

Abstract

Pretreatment with oral tadenan (TAD) has been shown to possess a protective effect on bladder dysfunction-induced obstruction. We evaluated the functional influence of cotreatment and post-treatment with oral TAD on the frequency/volume characteristics of micturition of conscious rats stimulated with exogenous dihydrotestosterone (DHT) to induce experimental prostate growth.Studies were done on 36 adult Sprague-Dawley male rats, treated daily for 6 weeks and grouped as follows: group 1, sesame oil during weeks 1 and 2, peanut oil during weeks 3 to 6; group 2, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle during weeks 1 and 2 and peanut oil during weeks 3 to 6; group 3, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle and TAD (100 mg/kg orally) in peanut oil during weeks 1 and 2 and TAD during weeks 3 to 6; and group 4, DHT in sesame oil during weeks 1 and 2 and TAD in peanut oil during weeks 3 to 6. The characteristics of frequency/volume were monitored biweekly and at the sixth week.Controls showed no significant changes from baseline values in volume or frequency during the entire study period. DHT treatment produced a significant increase in frequency (1.9 +/- 0.3 to 3.0 +/- 0.4/hr) and a significant decrease in volume (1.8 +/- 0.3 to 1.2 +/- 0.1 mL). In groups 3 and 4, no significant changes occurred in frequency or volume. By the sixth week of observation, the effects of DHT treatment decreased to control values in all groups. A significant increase in prostatic weight (1191 +/- 11 to 1434 +/- 17 mg/kg) was produced by DHT treatment and TAD cotreatment suppressed growth to 1390 +/- 8.4 mg/kg.TAD cotreatment or post-treatment suppressed the effects of DHT on micturition, and TAD cotreatment regressed a developing increase in prostatic weight. Post-treatment TAD administration did not reduce already established growth.

Abstract

To examine the effects of N-methyl-D-aspartate (NMDA) receptor antagonists on the frequency/volume (F/V) characteristics of micturition of conscious and anesthetized rats in relation to the mechanisms of renal urine output and pyelo-ureteral transport function of the upper urinary tract.Micturition F/V characteristics of 24 conscious female Sprague-Dawley rats, each weighting 160-180 g, were evaluated in a metabolic chamber. Control values of (F/V) were first obtained after administration of a 5-mL loading dose of saline solution and compared with intraperitoneal (i.p.) injection of 0.3-6.0 mg/kg of LY274614 (LY) and 0.3-40 mg/kg of dextromethorphan (DEX). Upper urinary tract studies were performed on two groups of urethane anesthetized rats (1.2 g/kg, s.c.). A group of 17 rats was used for intravenous (i.v.) injection of 1-30 mg/kg of LY and 1-10 mg/kg of DEX. In a second group of 12 rats, 0.2 mg/kg of LY and DEX were administered intracerebroventricularly (i.c.v.), by placing a catheter into the third ventricle. In anesthetized rats, continuous cystometrograms (CMG) were done while perfusing the renal pelvis with indigo carmine, and measuring pelvic and arterial pressure and as well as visualizing the transport of urine within the upper urinary tract by using videomicroscopic imaging.In conscious rats, the i.p. injection of LY and DEX produced a significant and dose-dependent increase in functional bladder capacity and a considerable increase in diuresis. In anesthetized rats, i.v. and i.c.v. administration of LY and DEX affected the micturition reflex, reflected as a significant increase in bladder capacity and preleakage pressure. Videomicroscopic imaging shows dilation of the ureter and a dilution of the dyed urine after the i.v. and i.c.v. injection of LY and DEX. The frequency of ureteral peristalsis and renal pelvic contractions were significantly decreased after i.v. and i.c.v. injection of LY as well as DEX.The present study shows that the NMDA receptor antagonists LY and DEX given systemically (i.v. and i.p.) or intracerebroventricularly influence the micturition reflex and modulate pyelo-ureteral motility as well as the rate of urine production. From the present study, it is suggested that NMDA receptors are directly involved in regulating pyelo-ureteral peristalsis as well as in the coordination of urine transport between upper and lower urinary tract.

Abstract

A urodynamic characterization of the distinctive patterns of normal micturition in man and rat was undertaken. Data were obtained from experimental studies where bladder pressure was measured suprapubically obviating urethral instrumentation. Ambulatory urodynamic studies were conducted with 17 asymptomatic male volunteers. Bladder pressure was monitored via a supra-pubic catheter and abdominal pressure via a rectal balloon using a UPS2020 ambulatory system. Average duration of each monitoring period was 20.5 hours. Detrusor pressure and flow rate records from each subject were identified and consecutive filling and voiding phases were averaged over the entire monitoring period using the onset of micturition as a time marker. The averaged pattern of pressure, flowrate, cumulative volume, and contractility curves for each subject as well each for group was computed and graphically presented. For comparison, the micturition phase of 18 anesthetized rats were used. A continuous CMG was performed and bladder pressure was recorded suprapubically. For each group the averaged parameters of urethral opening pressure, Max Detrusor pressure, Detrusor pressure at Max flowrate, bladder capacity, and WF were extracted and compared statistically. Numerical values are M +/- SE. The urodynamic temporal patterns observed during the micturition phase of the CMG in terms of detrusor pressure and associated flow, in both man and rat posses striking qualitative similarities. These are particularly striking during the onset of micturition in the great majority of animals. Furthermore the pressures generated by the bladder before and during micturition are quantitatively similar. However there were also distinct differences particularly in the pattern observed during voiding when bladder pressure was oscillatory. The temporal sequence of detrusor pressure and flow in man and rat contains many qualitative and quantitative similarities rendering the rat's potential as a particularly useful model in the study of the onset of micturition.

Abstract

Urodynamic characterization of normal male micturition can be a useful standard in the analysis of data on patients complaining of voiding dysfunction. The validity of such a standard is based on the need to obtain baseline parameters of pressure flow values, an important consideration when evaluating prostatic obstruction and its treatment. While current numerical pressure flow values provide a useful summary of the voiding sequence, a more complete analysis of the pattern of normal voiding may reveal more functionally useful information concerning micturition. We establish basic experimental conditions that simulate normal voiding of physiologically produced urine by the kidneys measured at intervals representing real stages of bladder filling. We report the results of an investigation designed to study consecutive micturitions at bladder volumes determined by water consumption and endogenous circadian rhythm. Our particular focus is to examine critically the urodynamic pattern of pressure flow and obtain evidence to support the hypothesis that fluid consumption has an important role in detrusor function.Urodynamic studies were conducted on 39 asymptomatic male volunteers with a mean age of 25.8 years (range 21 to 31) and mean weight of 75.5 kg. (range 63 to 95). Volunteers were divided into 2 groups according to water consumption regimen of 30 ml./kg. daily (17 patients, group 1) and 60 ml./kg. daily (12, group 2). Bladder pressure was monitored via a suprapubic catheter and abdominal pressure was measured via a rectal balloon using an ambulatory system. Average duration of each monitoring period was 20.5 hours. Detrusor pressure and flow rate records from each subject were identified, and consecutive filling and voiding phases were averaged during the entire monitoring period using the onset of micturition as a time marker. The average pattern of pressure, flow rate, cumulative volume and contractility curves for each subject, as well each for group, was computed and graphically presented. For each group the average parameters of urethral opening pressure, maximum detrusor pressure, detrusor pressure at maximum flow rate, bladder capacity and bladder contraction strength were calculated and compared statistically. Numerical values are mean +/- SE.Water consumption and urine production rate influenced the pattern and many of the urodynamic parameters of micturition. In both groups there was a detrusor pressure increase before voiding and numerically maximum detrusor pressure consistently occurred before micturition started. Micturition pattern showed an asymptotic relationship between pressure and flow. Doubling of water consumption increased urethral opening pressure from 51.2 +/- 3.2 to 61.5 +/- 5.1 (p <0.05), maximum detrusor pressure from 58.9 +/- 4.5 to 70.0 +/- 6.2 cm. H(2)O (p <0.01) and contractility from 15.4 +/- 1.4 to 17.7 +/- 1.4 w/m(2). There were no significant differences due to water consumption in maximum flow rate (24.4 +/- 1.4 to 25.2 +/- 1.8 ml. per second) or bladder capacity (286 +/- 20 to 329 +/- 15 ml.) but a significant increase in the number of micturitions from 5.8 +/- 0.5 to 9.8 +/- 0.5 per day (p <0.001) proportional to water consumption.The configuration of the observed pressure flow characteristics of the normal male is suggestive of the "Starlings law" relationship and the pattern of the urodynamic parameters were markedly different from those reported in the current standardization literature, suggesting the need to revise the current concept of normal male micturition. Voiding pressure and contractility increased in accordance with water consumption and urine production.

Abstract

The management of complex micturition problems frequently encountered in patients with spinal cord injury (SCI) may be facilitated by characterization of the elastic properties of the prostate. To this end, we have developed a method of evaluating changes in prostate biomechanics using ultrasound (US) images obtained during routine diagnostic urodynamic evaluations. Ultrasound video sequences of the prostate and urethra during voiding were digitized simultaneously with bladder pressure measurement on 76 patients with spinal cord injury, having a mean age of 47 +/- 16 years. Computer enhancement of the bladder/prostate/urethral interface from sequences of 2-D US images facilitated measurement of midprostatic urethral displacement during micturition. Of 76 patients, 21 were able to initiate voiding. Maximum urethral diameter was 12.0 +/- 1.3 mm, with corresponding maximum voiding pressure of 61.6 +/- 1.9 cmH(2)O. Urethral/prostatic pressure strain elastic modulus (Ep) was 960 +/- 624 N/m(2) and stiffness (beta) calculated as the inverse of compliance was 2.8 +/- 0.1. The diameter of the urethra at P(det50+), during the opening phase, was 0.4 +/- 0.1 mm and, during the closing phase, was 0.7 +/- 0.1 mm. During voiding, the anterior prostate was displaced to a greater extent than the posterior prostate. These observations suggest that distension of the prostate/urethra during micturition is hysteretic and nonuniform and indicates regional differences in compliance within the prostate/urethra interface. These regional differences lend support to the concept that the posterior prostate is implicated in the active process of micturition involving the fibromuscular stroma. Clinical application of this method could include quantification of the biomechanics of micturition consequent to spinal injury, prostatic enlargement, and the impact of targeted evaluation of pharmacological interventions.

Abstract

To: (i) visualize the effect of sustained voluntary contractions on the anatomical configuration of the pelvic floor (PF) muscles using magnetic resonance imaging (MRI); (ii) examine the effect of ageing on the range of displacement of the PF contents secondary to contraction and simulating incontinence exercises; and (iii) introduce the concept of contractile change in volume (DeltaPF-V) using three-dimensional (3D) reconstruction from axial, sagittal and coronal MRI.Two groups of continent women volunteers, familiar with correct PF contraction, were evaluated. The mean (sd) age in group I was 34 (6) years and that of group II 55 (9) years; the mean parities were 0.7 and 2.2, respectively. MRI was conducted with the women supine and data were obtained in the axial, sagittal and coronal planes. In each plane, images were obtained with the PF relaxed and subsequently with the PF contracted over 10-20 s. Image processing was used to enhance the anatomical boundaries of the pelvic organs and to measure the displacement produced by the contraction. Displacements, observed between each image pair, were colour-coded to highlight the geometric differences between a relaxed and contracted PF and to facilitate measuring displacement. Data measured from each group were pooled and the range of motion expressed as the mean (sd), compared using Student's t-test.Digitally processed imaging allowed an accurate comparison between the relaxed and contracted PF, and highlighted the differences between them. From these views, the levator ani displaced the vagina asymmetrically in nine of the 11 older subjects, and in six of the 17 younger subjects. The values from the imaging in the sagittal and coronal plane for the two groups were: levator ani displacement, 7.4 (1.1) and 1.4 (0.2) cm (P < 0.002), superior bladder wall, 4.2 (0.5) and 1.0 (0.1) cm (P < 0.002). There were also significant differences in the range of displacement produced by voluntary PF contraction in the internal structures; external outlines did not reflect these changes. The maximum displacement of the gluteal surface in the coronal plane did not change significantly; in group I it was 3.9 (1.8) to 2.9 (0.7) cm. From the 3D re-construction, DeltaPF-V for the younger women was significantly larger, at 23.3 (3.9) mL (P < 0.01) than in the older women, at 9.1 (4.4) mL. CONCLUCION: The range of motion over which voluntary PF contractions displace the bladder and vagina is age-dependent, being higher in younger than in older subjects. It remains to be established whether range of movement is a limitation caused by neuronal factors, decrease in muscle strength/mass, or the substitution of spaces with fat (restricting free movement), or other factors.

Abstract

The diurnal variation in the frequency/volume characteristics of male and female conscious rats was evaluated with reference to fluid consumption and urine production. Baseline values of the micturition volume and frequency of nine male and 10 female SD adult rats were measured over a 24-hour time period. The level of initial hydration conditions was standardized with 5 ml of water administered orally. With animals in a metabolism chamber having free access to water, the total volume of water consumed, the frequency/volume characteristics during micturition and the urine production rate were derived from the measurements of voided volume as detected by a digital balance. To establish reliability of measurements two separate micturition studies were done per rat at an interval of 1 week. Mean frequency of micturition and mean volume voided per micturition and urine production rate were computed in 3-hour time bins and represented over the 24-hour period. In addition the mean values of the number of micturitions and mean micturated volumes during the day/dark cycle were evaluated. The results show significant gender specificity in water consumption, urine production, and diurnal variations in micturition frequency/volume characteristics. Females consistently consume significantly larger amounts of water (83%) than males while urine production rate was correspondingly higher in females. It is concluded that water consumption and urine production are gender-specific. Because higher volumes of water are imbibed by females than males, the frequency/volume characteristic of micturition in the rat is also gender-specific. Data suggest that the volume voided per micturition depends on the urine production rate.

Abstract

To evaluate the effect of the oral administration of tolterodine on the diurnal micturition characteristics of the male and female conscious rat, and to examine the relative effect of tolterodine in influencing water consumption and urine production.Baseline micturition volume and frequency characteristics of nine male and 10 female Sprague-Dawley age-matched adult rats (body weight 399 +/- 15 and 249 +/- 3 g, respectively) were evaluated over 24-h. Initial hydration conditions were standardized with an oral dose (5 mL) of water. Rats were subsequently placed in a metabolic cage and had free access to water. Micturition volume/frequency characteristics were derived from the measurements of voided volume (measured using a digital balance below the metabolic cage and connected to a computer). The total volume of water consumed over the 24 h was also measured. Two separate baseline studies were conducted, followed by the administration of a single oral dose of 1 mg/mL of tolterodine dissolved in 5 mL of water. The mean frequency of micturition and mean volume voided per micturition were computed in 3-h periods and plotted over the 24-h period. In addition, the mean values of the number of micturitions and voided volumes during the day/dark cycle were evaluated.Baseline data showed that females (when corrected for body weight) consistently imbibed significantly more water (83%) than did male rats. Tolterodine did not significantly affect water consumption in the males but significantly reduced water consumption in females by 42%. Tolterodine did not significantly affect the amount of urine produced by male rats but significantly reduced the total amount of urine production in females by 26%. Tolterodine significantly increased the number of voids in male rats compared with baseline during the day but not during the night. More importantly tolterodine produce no significant effect on the volume voided per micturition in male rats either during the day or night cycle, but significantly decreased the volume voided per micturition in females.These results suggest that the effect of tolterodine on micturition is gender-specific, suppressing water consumption and urine production in female but not male rats, and decreasing bladder volume. There is a possibility that the reported clinical effects of tolterodine arise through the suppression of fluid consumption.

Abstract

To evaluate the effect of Tadenan (TAD; Pygeum africanum extract) pretreatment on the micturition characteristics of conscious and anesthetized rats consequent to dihydrotestosterone (DHT) administration and to examine the influence of such treatment on the growth of the prostate.Studies using 40 adult Sprague-Dawley male rats were performed during a 7-week period. These animals were treated with DHT 1.25 mg/kg subcutaneously dissolved in peanut oil and/or TAD 100 mg/kg orally dissolved in sesame oil, except for the controls, which received vehicle only. Rats were divided into four groups: group 1 (control), vehicle only; group 2, DHT administered during weeks 3 and 4; group 3, TAD pretreatment, administered during weeks 1 and 2, followed by the combined administration of DHT and TAD during weeks 3 and 4 and TAD only during weeks 5 to 7; and group 4, continuous TAD treatment for 7 weeks. Micturition of conscious rats was evaluated in metabolic chambers, and in anesthetized rats, cystometrograms were done at the end of 7 weeks.DHT or DHT plus TAD did not produce significant changes in the volume but did reduce the frequency of micturition. TAD given alone significantly increased the volume of micturition and the rate of urine production. Cystometrographic studies in anesthetized rats revealed that DHT produced micturition characteristics similar to obstruction. The DHT plus TAD and TAD pretreatment data showed no significant difference from controls, suggesting that in the presence of TAD, the effects of DHT were negated. The total prostate weight of DHT and DHT plus TAD pretreated rats increased, and in the TAD group, these values decreased to lower than controls; growth of the ventral lobes was suppressed in the presence of TAD.These results demonstrate that TAD pretreatment significantly reduces the "obstructive" effects of DHT on micturition, counteracts the hormone-induced enlargement of the prostate, and reduces prostate weight in the ventral but not the dorsal lobe.

Abstract

The age related effects of 17beta-estradiol (E) supplementation on micturition and contractility of ovariectomized rats (OVX) were evaluated. Studies were carried out in young, 2 month, and mature, 10 month old rats which were distributed into three groups: Sham-operated (SHAM), (OVX), and (OVX+E). Following treatment, urodynamic studies were performed followed by an in vitro bladder tissue evaluation. Urodynamic studies show age and time related changes in bladder function. The in vitro results show that the hormone deprived tissues of 2 months old rats had a decreased responsiveness to cholinergic stimulation; maximum contractile force occurred at 78% and 187% for the SHAM. The response from the OVX+E tissues was evident at 113%. E supplementation of the mature rats increased bladder contractile force to the same levels as SHAM (156% and 176%). The response of the mature OVX rats remained significantly below that of SHAM or OVX+E rats. Findings suggest that the impact of E on bladder function depends on age at which it is given. Differential response between young and mature to exogenous E indicates that endogenous estrogen plays a major role in the neuromuscular development of normal bladder function and micturition reflexes. Contractility data show that OVX in young rats irreversibly decreases the response of the bladder to cholinergic stimulation, suggesting that exogenous E partially restores function while in mature rats, exogenous E was able to reverse the effects of OVX.

Abstract

The purpose of this study was to evaluate the impact of chronic urinary tract obstruction which was produced in the rat using neurohormonally induced experimental prostate growth. In this model, we considered the chronology of changes in the micturition characteristics of awake rats relative to prostate weight and stiffness. The corresponding urodynamic characteristics of both the upper and lower tracts were evaluated in anesthetized animals relative to the development and extent of the obstruction produced. Prostate growth was produced by capitalizing on the synergistic properties afforded by the combined administration of dihydrotestosterone propionate (DHT) and the alpha1 adrenoreceptor antagonist prazosin (PRZ). DHT (1.25 mg/kg/day) was dissolved in 0.1 ml sesame oil (SO) and coadministered with PRZ 30 microg/kg/day subcutaneously for 14 days to 12 experimental rats. SO alone was given to 8 control rats. Micturition studies were first performed using all 20 awake rats, which were placed unrestrained in metabolic cages. Urodynamics of the upper and lower urinary tracts were repeated following anesthesia at the 5th, 10th, and 15th weeks after initiation of hormonal or SO treatment. Following the urodynamic studies, the rats were killed and prostates were removed and weighed, and stiffness was measured. Studies with awake rats show that hormonal treatment produces a significant and progressive increase in mean frequency of micturition, ranging from 0.63+/-0.16 in controls and reaching the maximum of 2.15+/-0.40/hr by the 10th wk. Results from urodynamic studies with anesthetized rats also show typical and progressive obstructive characteristics: maximum detrusor voiding pressure (Pdetmax) increased from 52.7+/-2.03 in controls to a maximum of 77.5+/-2.2 cm H2O by the 10th week; urethral opening pressure Puo likewise increased from 52.6+/-2.7 in controls to 73.3+/-2.1 cm H2O in experimental rats. The duration of time during which the detrusor sustains contraction during voiding also rose, from 16.8+/-1.8 sec in controls to 32.0+/-3.2 sec by the 10th week. There were no significant changes in bladder capacity, baseline filling pressures, or arterial pressures. Prostate weight increased significantly from 0.76+/-0.05 g in controls to 1.17+/-0.1 g by the 15th week. Similarly, stiffness increased from control values of 1.33+/-0.18 g/cm to a maximum of 3.59+/-0.14 g/cm by the 10th week. It is concluded that neurohormonally stimulated prostate growth in the rat is a suitable animal model for the study of the development of urinary tract obstruction. Obstructive characteristics were validated in both awake rats by the increase in the frequency of micturition and urodynamically under anesthesia in terms of elevations in maximum detrusor pressures, urethral opening pressure, detrusor contraction time, and prostatic stiffness. The effect of obstruction was further shown to be associated with vesicoureteral reflux during micturition and elevated upper tract pressures.

Abstract

In this investigation, we examined the impact of the alpha1 adrenoceptor (alpha1-ADR) antagonist prazosin on the urodynamic characteristics of upper urinary tract function and associated micturition characteristics of the adult male rat. The focus of the study was to evaluate the extent to which prazosin affects urine production and ureteral transport relative to its effect on micturition. Control micturition studies were first performed using 28 awake Sprague-Dawley rats that were placed in metabolic cages for characterization of the frequency and mean and total volume voided over a 4-hr period. Following the control studies, the effect of intraperitoneal prazosin, 30 microg/kg, was evaluated under identical conditions. Urodynamic studies were done to identify the bladder filling and voiding characteristics of anesthetized rats that were infused with saline at a rate of 0.22 ml/min. From the urodynamic studies the parameters of bladder pressure (Pves) and volume (V) during filling, urethral opening (Puo) measured at the moment of micturition, and maximum detrusor pressure during voiding (Pdetmax) were evaluated. External sphincter electromyography was also monitored and recorded together with bladder pressure during voiding. Renal pelvic pressure was measured via a nephrostomy catheter and recordings were made simultaneously with bladder filling and voiding. The upper urinary tract was visualized using microscopic video imaging of the ureter, contrasted by perfusing the renal pelvis with indigo carmine. Characterization of upper tract transport was made in terms of renal pelvic pressure, ureteral peristaltic rate, and bolus length and velocity. The results show that in the awake rat, 30 microg/kg of prazosin decreased the urine production rate from 4.8 +/- 0.074 to 1.6 +/- 0.23 ml (P < 0.001) and micturition frequency by a similar proportion from 1.99 +/- 0.44 to 0.53 +/- 0.08/hr. In the lower urinary tract, prazosin did not change the baseline pressure of the bladder but produced significant dose-dependent decreases in Pdetmax, Puo, and frequency of micturition. In the upper urinary tract, ureteral and pelvic frequencies decreased, whereas the length of bolus increased significantly corresponding to increased doses of prazosin. These results suggest that, although prazosin facilitates micturition by reducing urethral opening pressure, it also reduces the rate of urine production and modulates the function of urine transport in the upper urinary tract.

Abstract

The effect of intrathecal (i.t.) baclofen in modulating the micturition reflexes, detrusor contraction strength, and micturition efficiency was evaluated in anesthetized rats.Female Wistar rats (n = 14, 337 +/- 8 gm.) were anesthetized with urethane (1.2 gm./kg. s.c.). Cystometrograms were done through a lower midline incision made to expose the bladder and a catheter was inserted through the bladder dome to record pressure during filling with saline at the rate of 0.038 ml./min. During the micturition phase of cystometrogram, the measurement of voided volume was made synchronously with the intravesical pressure. Baclofen was given intrathecally at the increasing doses of 0.05, 0.10, 0.5 microgram. and pressure/flow parameters were measured.The measured urodynamic parameters show that baclofen produced a significant dose dependent increase in bladder capacity and a decreases in voiding efficiency, detrusor pressure and maximum and average flow rate. Baclofen (0.1 microgram.) significantly decreased detrusor contractility reducing both Wmax from 3.7 +/- 0.1 (control) to 2.0 +/- 0.1 W/m2 and Wisv,max from 5.9 +/- 0.3 to 5.5 +/- 0.4 W/m2 respectively. Baclofen altered the characteristic pattern of the micturition reflex by suppressing high frequency pressure oscillations during voiding which was completely abolished after 0.1 microgram. in 75% of the rats. Furthermore, urinary dribbling incontinence was evident at a dose of 0.5 microgram. in 58% of all rats.These results demonstrate that i.t. baclofen has a significant inhibitory effect on the micturition reflex, depressing detrusor contraction strength and micturition efficiency, while increasing bladder capacity.

Abstract

The stiffness characteristics of the empty and filling bladder and the modulating influence of oxybutynin were investigated using a new biosensor system. Studies were done comparing the stiffness measured using the pressure/volume relationship with direct biosensor monitoring on male and female rats during isovolumetric contractions elicited during the cystometrogram (CMG). Bladder stiffness at zero volume, measured in vitro using the biosensor, was evaluated and compared with the stiffness of the prostate, seminal vesicles, testicles, and uterus. In 5 small anesthetized male rats, in vivo isovolumetric studies were performed and bladder stiffness was measured during the storage and contraction phase of the CMG. In 6 mature female rats, change in bladder stiffness during isovolumetric contractions was investigated following intraarterial (i.a.) administration of 0.1 and 1.0 mg/kg of oxybutynin. After the in vivo CMG was completed, an in vitro CMG was done measuring bladder stiffness. The results show that bladder stiffness, measured during the storage phase of the CMG, increased in accordance with the stretched length of bladder wall. During the in vivo CMG, bladder stiffness increased consequent to a spontaneous contraction from 10.0 +/- 1.9 g/cm to 29.9 +/- 3.0 g/cm (P < 0.005). Oxybutynin produced a significant decrease in bladder stiffness during the storage phase of the CMG, as measured using the biosensor, which was concomitant with an increase in bladder compliance derived from pressure/volume data. The incremental change in stiffness, delta K, during isovolumetric contraction decreased due to i.a. oxybutynin in accordance with a decrease of maximum detrusor pressure. These results indicate that delta K is related to the active change of viscoelastic properties of bladder smooth muscle. These findings imply that direct measurement of the stiffness of the bladder wall possesses the potential to be an objective assessment of bladder biomechanical properties and of their functional response to obstruction and pharmacological intervention.

Abstract

Videomicroscopic imaging of the upper urinary tract was performed in 26 female anesthetized rats during bladder filling and micturition. Recordings were made of the pressure of the renal pelvis through a nephrostomy and visualization of the dynamics of the ureteral bolus. Peristaltic velocity, frequency, bolus length, and direction urine bolus propagation were derived on the basis of image processing using indigo carmine for contrast. In addition, nonstop cystometrograms were performed at an infusion rate of 0.22 ml/min characterizing bladder filling and micturition reflexes. Using this setup the pharmacological response of the upper and lower urinary tract dynamics to intravenous oxybutynin and LY274614 was evaluated and compared to observations made with placebo time controls. The data, obtained from the time controls, indicate that there is a significant time-dependent influence on the upper urinary function caused by the experimental methodology in the frequency of ureteral peristalsis and length of the bolus. Oxybutynin produced a significant increase in the length of the but not in the velocity of the bolus. LY274614 depressed pelvic pressure and ureteral frequency and increased bolus length. It is concluded that videomicroscopic imaging, in association with nonstop cystometry, provides a unique method to investigate the pharmacological effects of centrally and peripherally acting drugs on the upper and lower urinary tract function without mechanical manipulation of the ureter.

Abstract

The influence of dihydrotestosterone propionate (DHT) and estradiol (E) on prostate growth and micturition was evaluated. Complete studies were carried out on 49 Sprague-Dawley rats over a 14-day period. Rats were divided into three groups: (1) controls, (2) DHT, and (3) DHT + E. All groups were injected daily with 0.1 ml of sesame oil, together with 1.25 mg/kg of DHT for group 2 and 1.25 DHT + 0.125 mg/kg E for group 3. Physiological measurements of micturition were done weekly by subcutaneously administering a fluid loading dose consisting of 10 mg/kg furosemide + 5 ml saline. Parameters of micturition frequency, volume, and prostate weight were calculated. Prostate weight values for controls were 0.89 +/- 0.06 g while those treated with DHT increased significantly to 1.26 +/- 0.10 g (P < 0.05) and those treated with DHT + E also increased significantly to 1.24 +/- 0.09 g (P < 0.05). There was no significant difference in prostate weight between the DHT and DHT + E groups. Analysis of micturition data shows that the mean volume voided per micturition decreases in both the DHT and DHT + E treated rats. At between 7 and 14 days of DHT and DHT + E treatment, rats micturated at significantly reduced mean volumes. The lowest mean volume per micturition was detected on the 14th day of DHT treatment, showing a significant reduction from control values of 3.05 +/- 0.27 to 1.68 +/- 0.05 ml. The corresponding value of the mean micturated volume in the DHT + E groups was 1.86 +/- 0.31 ml. Control values for frequency of micturition was 3.25 +/- 0.52/hr, while for rats treated with DHT it was 3.62 +/- 0.38/hr and for DHT + E it was 4.0 +/- 0.54/hr. Evidence is provided to demonstrate that 14 day DHT, and particularly DHT + E, stimulation produces significant alterations in prostate weight and micturition characteristics of unanesthetized rats. On the basis of these observations it is proposed that the hormonally enlarged prostate promotes stimuli to trigger the spinal micturition reflex, thereby producing increased frequency of micturition.

Abstract

A new in vivo urodynamic animal model was developed to analyze the micturition characteristics of the rat. This model was used to study the modulating effect of pharmacological agents on vesicourethral function, using cystometry and uroflowmetry. Pressure-flow studies were done in 25 female rats anesthetized with urethane. Filling cystometry was recorded using a physiological rate of bladder filling through transvesical infusion. Micturition characterization was done by identifying the time course and amount of voided volume. Voided volume was measured by a novel application of a mechanotransducer, which provided the data to measure flow rate and compute the voided volume-time curve. Flow rate was calculated by differentiating the curve produced by the mechanotransducer. Using this system, comparative tests of pharmacological stimulus were done using anticholinergic stimulation, alpha 1, and a new N-methyl-D aspartate (NMDA) receptor antagonist. The effects of the intravenous use of these drugs in the lower urinary tract were evaluated at various dose levels. The results showed that anticholinergic stimulation produced an increase of bladder capacity and decreases of detrusor pressure and maximum flow rate. Although the alpha 1 blocker decreased detrusor pressure, flow rate did not change significantly. By contrast, NMDA receptor antagonism produced a depressant effect on bladder reflex contraction, and increased bladder capacity in a dose-dependent way. However, maximum flow rate increased at a dose of 10 mg/kg and decreased at 30 mg/kg significantly. These results suggest that a decrease in flow resistance through the outlet region was due to the effects of NMDA receptor inhibition at lower doses. In conclusion, this model enables the evaluation of drugs regarding lower urinary tract function and provides in small animals the possibility of evaluating the relationships between pressure and flow in various experimental models.

Analysis of the relative biomechanical effects of alpha 1 and alpha 2 antagonists in modifying the compliance of the prostate and micturition parameters of the hormonally manipulated male ratNEUROUROLOGY AND URODYNAMICSConstantinou, C. E., Omata, S.1996; 15 (1): 85-101

Abstract

The potential of the alpha 1 and alpha 2 antagonists to modify prostate compliance, and micturition characteristics of rats with hormonally enlarged prostates was studied. Prostate growth was induced in Sprague-Dawley rats using dihydrotestosterone (DHT) and estradiol (E) by daily subcutaneous injections of DHT 1.25 mg/kg and E 0.25 mg/kg together with 0.1ml of sesame oil, as a vehicle, for a period of 3 weeks. A control group of six rats was used wherein the vehicle alone was administered. Dose levels of 3, 10, 30, and 300 micrograms/kg of alpha 1 or alpha 2 antagonist were given at weekly intervals to each of the groups defined above. Voiding characteristics, in terms of micturition frequency and volume per micturition, were measured and correlated with the pharmacological and hormonal stimulus. Prostate compliance and weight was evaluated in each of the groups after rats were terminated and the ventral prostate was dissected and removed in in toto. Compliance measurements were made using a new biosensor system which is based on the principle of detecting the shift in the resonance frequency of the biosensor produced by the hormones on the acoustic impedance of prostate. The results show that DHT and [DHT+E] significantly increased prostate weight and decreased prostate compliance. The alpha 2 antagonist atipamezole significantly increased the compliance of all prostates, including controls, while the alpha 1 antagonist did not alter the compliance. It is concluded that this alpha 2 antagonist is more effective than the prazosin in reversing the hardening effect of hormones on the prostate.

Abstract

We describe a new methodology for direct ex vivo measurements of corporal stiffness. Using a new biosensor, stiffness of the corpora cavernosa was measured in 32 mature male Spraque Dawley rats. Mean stiffness (+/- se) value of the corpora was 8.186 +/- 0.318 gm/cm. The corpora was numerically the stiffest organ, when compared to the bladder and the prostate. Values measured at different points from both corpora showed a quite uniform stiffness (range 7.576-8.835 gm/cm). Hormonal stimulation with DHT was shown to significantly increase prostatic stiffness but not corpora stiffness. Similarly alpha-adrenergic antagonists did not affect corporal stiffness in a statistically significant manner. These results suggest that the influence of hormones and adrenergic stimulation on the passive properties of the corpora is negligible. It is concluded that this new method provides a reproducible new parameter for the measurement of corporal stiffness. It is anticipated that in the future this kind of stiffness measurement may be of use for the evaluation of the biomechanical properties of the corpora and its response to pharmacologic manipulation of the trabecular smooth muscle tone in vivo.

Abstract

We present a biosensor intended to evaluate prostatic stiffness. The stiffness of the prostate was modulated using hormonal induction and adrenergic stimulation. The results show that the sensor can be sufficiently accurate to discriminate between soft prostates used as controls and those stiffened with hormones. The modulation produced by an adrenergic agent on prostatic stiffness was detected using this system. An electrical model was constructed embodying the parameters of prostatic stiffness, micturition frequency, and volume, demonstrating that prostatic stiffness correlates with micturition frequency.

Abstract

Magnetic resonance was used to visualize the effect of voluntary pelvic floor contractions on the abdominal structures with particular emphasis in determining the dynamic relationship between the bladder and surrounding organs. The pelvic floor was imaged in 6 asymptomatic female volunteers using MRI viewed in seven coronal and seven sagittal planes. The relative displacement of the bladder resulting from voluntary pelvic floor contraction was measured and the changes from the relaxed to the contracted stage were identified. Measurements from sagittal images show superior bladder wall movement of 3.8 +/- 1.3 mm, posterior of 7.0 +/- 2.8 mm, while maximum movement in the gluteal region was 3.5 +/- 4.0 mm. The results show that voluntary contractions of the pelvic floor measured and visualized using this technique can be identified and displayed using image processing techniques. Anatomical displacement of the bladder in the superior direction is illustrated, demonstrating that pelvic floor contraction provides increased levator muscle support. There is no significant displacement of the anterior aspect of the bladder, while the posterior wall demonstrates maximum movement.

Abstract

To assess the ability of serum prostate specific antigen (PSA) to predict and differentiate patients with normal and abnormal digital rectal findings.A prospective analysis of 1374 participants in a prostate cancer screening programme was performed. After completion of a questionnaire including age and voiding symptoms as well as phlebotomy for PSA analysis, digital rectal examination was performed and the findings were categorized with respect to size, consistency, symmetry and nodularity.In men less than 50 years of age the mean serum PSA level failed to discriminate any of the digital rectal examination categories. In men over 50 there was a statistically significant difference in mean PSA levels between symmetrical, normal sized prostates and symmetrically enlarged glands as well as between symmetrical, normal sized and abnormal prostates (P < 0.05). No statistically significant difference was found in mean serum PSA levels between symmetrically enlarged prostate glands and those with palpable nodules. PSA levels < or = 2.5 ng/ml (normal range for the Yang polyclonal assay) and < 7.4 ng/ml (corresponding to the normal range of < 4.0 ng/ml for the Hybritech monoclonal assay) demonstrated a probability of an abnormal digital rectal examination of 11% and 14% respectively. PSA levels > 18.4 ng/ml (corresponding to monoclonal levels of > 10 ng/ml) had a 67% probability of an abnormal digital rectal examination. However, moderate elevations in PSA could not be used to predict digital examination abnormalities due to the high incidence of moderate PSA elevations associated with symmetrical enlargement of the prostate.Serial annual PSA measurements may provide an alternative means of screening men over 50 years of age. Contamination of results with PSA elevation due to benign prostatic hyperplasia remains, however, a problem.

THE EFFECT OF ALPHA2 AGONISTS AND ANTAGONISTS ON THE LOWER URINARY-TRACT OF THE RATJOURNAL OF UROLOGYHarada, T., Constantinou, C. E.1993; 149 (1): 159-164

Abstract

The pharmacologic potential of selective alpha 2 adrenergic agents in modulating vesicourethral function was evaluated in urethane-anesthetized and conscious rats. The bladder was exposed through a midline incision and intubated via a cystostomy to measure pressure. The bladder was filled with saline at 0.05 ml./min. In six animals intravenous dexmedetomidine 0.6 micrograms./kg. followed by 2 micrograms./kg. was given. In another six rats the infusion was made with atipamezole at the same concentration. The parameters obtained were pressure/volume during cystometry, detrusor voiding pressures, and evidence of urine leakage. Conscious rats were placed in a restrainer outfitted with a voided volume sensor and a data recorder. The animals were divided in three groups. In controls, group I (n = 8), the animals were injected with a subcutaneous (SC) load of 5 ml. saline in which furosemide 10.0 mg./kg. was added. In group II (n = 6), dexmedetomidine was added in group III (n = 6), atipamezole was added. Parameters obtained were volume per micturition, latency, frequency of micturition, and patterns of micturition (such as dribbling), and total volume produced after a three hour recording. Values are expressed as mean +/- standard deviation. The results show that in an anesthetized preparation, the alpha 2 agonist dexmedetomidine produced inhibitory effects on the volume evoked micturition reflex (VEMR) at a dose level of 2.0 micrograms./kg. There was a significant decrease in peak pressure from 26.4 +/- 3.6 to 6.8 +/- 2.1 cm. H2O (p < 0.01). Urine leakage was observed at the external meatus. Atipamezole, the alpha 2 agonist, gradually increased bladder baseline pressure and inhibited VEMR. At a critical pressure there was continuous leakage from the external meatus. There was a significant elevation of baseline bladder pressure by atipamezole from 6.3 +/- 1.7 to 29.8 +/- 4.6 cm. H2O (p < 0.005). In conscious rats, the alpha 2 agonist produced urinary dribbling at approximately 20 minutes after SC injection, while the antagonists produced delayed dribbling 70 minutes after SC injection. Leakage occurred in 3 of 6 rats at a dose of 10 micrograms./kg. of atipamezole and in 5 of 6 rats at a dose of 30 micrograms./kg. The alpha 2 agonist caused a diuretic effect and a dose-dependent increase in the frequency of voiding (p < 0.05), while the antagonist decreased the frequency of voiding. Bladder capacity was decreased with the alpha 2 agonist while the antagonist increased capacity.

THE EFFECT OF BACTERIURIA ON BLADDER AND RENAL PELVIC PRESSURES IN THE RAT1991 ANNUAL MEETING OF THE SECTION OF UROLOGY OF THE AMERICAN ACADEMY OF PEDIATRICSIssa, M. M., Shortliffe, L. M., Constantinou, C. E.ELSEVIER SCIENCE INC.1992: 559–63

Abstract

We investigated the effect of urinary tract infection on bladder and renal pelvic urodynamics in a rat model to examine the role of pressure during infection. Either an antibiotic solution (control group) or Escherichia coli with type 1 pili (infected group) was instilled into the bladder. After 2 to 6 days simultaneous continuous bladder and renal pelvic pressures were measured during urinary flows from less than 2 to greater than 20 ml./kg. per hour while the bladder filled and emptied. Bladder pressures from 50 to 100% of maximum capacity and maximum voiding pressures were significantly higher in the infected group than the control group (36.7 +/- 6.79 cm. water versus 25.5 +/- 5.21 cm. water, respectively, p less than 0.0001). Renal pelvic pressures were significantly higher in the infected group during bladder filling at all urinary flows examined and actually exceeded bladder pressure for the highest flows. We conclude that elevated renal pelvic pressures may contribute to renal changes observed during urinary tract infection.

Abstract

We report here the results of a simplified screening method to rapidly compare the pharmacologic action of drugs relevant to the urinary tract. This method avoids the use of anesthesia and of external infusion into the bladder relying on the physiological stimulation of the volume-evoked micturition reflex (VEMR) by diuresis. Mature female rats weighing 240-310 g were placed in restrainer cages that afforded access to food and water but limited movement. Under the rear of the rat, a collecting funnel and weight measuring device was secured. For each VEMR, the weight of the volume voided was recorded on a polygraph which also provided a record of the time of voiding. To evaluate the relative pharmacologic efficacy of the drug under study, 1 mg/kg furosemide along with the drug to be evaluated was diluted in 5 ml of saline and injected subcutaneously. Rats received approximately equimolar concentrations of thiphenamil and 15 other analogs, Ca2+ channel blockers, and K+ channel openers. The furosemide was given to obtain a controlled level of diuresis and avoid the effects of circadian variations in urine flow. Parameters considered were 1) mean volume voided per VEMR, 2) frequency, 3) output, and 4) latency. This model allows the rapid evaluation of drugs designed to increase bladder capacity and decrease the frequency of voiding, and it is particularly useful in evaluating the relative efficacy of drugs that are chemical analogs.

Abstract

The contractile characteristics of pacemaker regions in the unicalyceal renal pelvis of the rabbit were examined in vitro. The amplitude and frequency spectra of spontaneous contractions of whole and separated circular and longitudinal renal pelvic strips were identified. The effect of stretch on these parameters were examined in order to establish whether the pacemaker region that generates contractions in the renal pelvis was sensitive to distention. The results show that the frequency of spontaneous contractions in the whole pelvis (65 +/- 18 mHz) was significantly higher than any part of the circularly (41 x 8 mHz) or longitudinally cut (43 +/- 8 mHz) pelvis. The amplitude of longitudinal strips, 52 +/- 11 mg, was significantly smaller than that of the circular strips, 267 +/- 52 mg. In the circularly separated pelvis the frequency of spontaneous contractions was highest in the proximal part (41 +/- 8 mHz) and lowest in the pelviureteral junction (8 +/- 1 mHz). No significant increase in frequency was seen upon stretch in the whole or separated pelvis although there was a decrease in the amplitude of both the whole and separated pelvis. These results show that the frequency of contraction of the whole or the segmented renal pelvis is not sensitive to stretch.

Abstract

A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment of detrusor incontinence using thiphenamil HCl in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks of thiphenamil HCl or placebo administration were followed by 1 week of washout followed by a cross-over to an additional 2 weeks of placebo or thiphenamil HCl administration. Of the 23 patients 7 dropped out at various stages of the study. The mean age of patients studied was 44 +/- 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time of voiding and the incidence of incontinence. Three urodynamics studies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters of bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the frequency of incontinence, which was based on the patients' responses, decreased significantly (0.01 less than p less than 0.025). There was an insignificant decrease in the number of voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing problems caused by urine loss during baseline and thiphenamil treatment, analysis shows a significant decrease of problems due to loss of urine (p = 0.01) when the patient was taking the drug compared to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

The effect of thiphenamil HCl on the urodynamic parameters of bladder filling, voiding and isometric contraction was examined in controls. Data were obtained from 25 control female subjects with a mean age of 27.6 +/- 6.6 years. Three urodynamic studies were done on each subject on 3 different days. These studies were: (1) control study, (2) drug study with a single oral dose of 400 mg thiphenamil HCl and (3) another with 800 mg. Each urodynamic study involved filling and voiding cystometrograms to characterize stability, sensations of fullness and urgency, bladder capacity, urethral opening pressure, maximum flow rate, maximum detrusor pressure and residual urine. In addition, isometric detrusor pressure measurements were made at bladder volume increments of 100 ml. Each urodynamic study was done in the sitting position using medium fill water cystometry at 20 ml/min. Isometric pressures were made by catheterizing the subject with an 18-french three-way Foley catheter with a 30-ml balloon. One lumen was used to fill the bladder and the second to measure pressure. The results show that bladder capacity and the volume at which sensations of fullness and urgency are expressed are not significantly changed under the influence of thiphenamil HCl. Significant differences were seen in the maximum pressure generated by the detrusor during voiding and in the maximum urine flow rate. These differences were most pronounced at the 800-mg thiphenamil HCl dose. The isometric data show a highly significant increase in the maximum isometric pressure developed at the low bladder volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

The pharmacologic effect of thiphenamil HCl on the upper urinary tract as a relaxant of renal pelvic contractions was studied. A total of 17 subjects with no known upper urinary tract abnormalities were scanned. A Diasonics ultrasound scanner at 3.5 MHz was used to visualize the kidney and renal pelvis with the subject in the supine position. Control recordings of renal pelvic and calyceal contractility were made on videotape for approximately 30 min. The subject was then given a single dose of 400 mg thiphenamil HCl and visualization of contractility continued for approximately 60-90 min. Criteria for the evaluation of the data were the mean frequency of pelvic contraction cross-section of the pelvis, and velocity and direction contraction. Ultrasonic images were filtered by a video filtering process and averaged using the digital conversion and summation in real time. The results show that under control conditions renal pelvic contractions are at a frequency of 2 +/- 1.8 min-1. Contractions are initiated with the intrarenal pelvis and continue towards the ureter at a rate of 1.3 +/- 0.8 cm/s. Following thiphenamil HCl, there is a significant reduction in pelvic contraction frequency, 0.6 +/- 0.6 min-1, and the opposing walls of the renal pelvis do not completely close in the formation of a bolus. The results obtained from this study demonstrate that thiphenamil suppresses upper urinary tract contractility. As a consequence of this observation, it is postulated that this agent may be of use in the acute relaxation of the upper urinary tract for renal colic and stone management.

Abstract

The circumstances facilitating hydrostatic pressure communication between the bladder and renal pelvis were evaluated. In particular, we compared active detrusor contractions occurring spontaneously during voiding and evoked contractions produced during electrical pelvic nerve stimulation with passive abdominal compression. These variables were evaluated with respect to urine flow rate and bladder capacity. Waveform analysis of the pacemaker characteristics of the renal pelvis shows that the rat pelvis has a narrow frequency band of spontaneous contraction at 0.5 +/- 0.06 Hz. The baseline waveform and pressure of the pelvis is effected by urine flow and bladder capacity. Significant elevations in pelvic pressure of 25.8 +/- 7.9 and 28.7 +/- 5.8 cm H2O were observed for bladder pressures of 30 cm H2O (n = 8) at flow rates in the range of 2.5-5.0 and over 5.0 ml/kg/h respectively (p less than 0.05). At flow rates between 2.5 and 5.0 ml/kg/h, spontaneous contractions produced an increase in pelvic pressure in all rats, while electrical stimulation produced an increase in pelvic pressure in 63%. At flow rates above 5 ml/kg/h, abdominal compression produced sharp elevations in pelvic pressure in 75%. At the same flow rate, electrical stimulation produced a slow increase in 75% and spontaneous contraction produced a slow increase in 86%. These results suggest that the exposure of the upper urinary tract to vesical pressures occurring during active and passive contractions is facilitated by flow.

Abstract

The impact of female sex hormones on the rhythmic urethral pressure variations (UPV) was analysed based on data from one hour urethral pressure recordings from 10 healthy fertile female volunteers measured three times during the menstrual cycle and from 12 healthy postmenopausal women measured twice within two months. The mean maximum urethral pressure (mMUP) and the mean maximum urethral closure pressure (mMUCP) had a median value of 66.5 (Interquartile 58.0-86.0) and 60.0 (49.0-80.0) cm.H2O respectively in the healthy fertile females. The postmenopausal women had a significantly lower mMUP and mMUCP of 55.5 (48.5-58.5) and 43.5 (35.5-47.0) cm.H2O) respectively. Rhythmic UPV was recorded inhealthy fertile and postmenopausal women. Frequency analysis of the UPV revealed a frequency spectrum from 0.0015 to 0.035 Hz on top of which were respiration fluctuations and vascular pulsations. The UPV amplitude was related to the mMUP and increased with increasing mMUP. The parameters analysed were stable during the menstrual cycle and during menopause. Thus no difference in the UPV frequencies or amplitudes was observed between the healthy fertile and the postmenopausal women. The investigation shows that the pressure variation in urethra apparently is not modulated by female sex hormones.

Abstract

The effects of the cyclooxygenase inhibitors indomethacin and acetylsalicylic acid (ASA) and the prostaglandin (PG) antagonist 1-acetyl-2-[8-chloro-10,11-dihydrodibenz (b,f)(1,4) oxazepine-10-carbonyl]hydrazine (SC-19220) on smooth muscle strips from the rabbit renal pelvis were examined. Circularly oriented tissues were taken from within the renal pelvis and subdivided into the four adjoining regions, from fornix to pelviureteric junction (PUJ). They were set in a tissue bath and isometric tension changes were recorded. Spontaneous contractions were observed and electrical field stimulations evoked twitch-like contractions. The frequency of spontaneous contractions was dependent on the region within the renal pelvis from which they were dissected, gradually decreasing from fornix (3.92/min.) to PUJ (0.43/min.). Indomethacin (10(-5)M) or ASA (10(-4)M) significantly increased the frequencies of spontaneous contractions in all four regions. In the upper three regions (pacemaker regions), both agents significantly decreased the amplitudes of spontaneous and stimulation-induced contractions. In the PUJ region, both agents significantly increased the amplitudes of spontaneous and stimulation-induced contractions. SC-19220 (3 x 10(-5)M) significantly increased the frequencies and decreased amplitudes of spontaneous contractions in all four regions. These results suggest that the PUJ has different contractile characteristics from those of pacemaker regions and that decrease of amplitude by indomethacin or ASA is based on their cyclooxygenase inhibitor property.

THE EFFECT OF URINARY FLOW AND BLADDER FULLNESS ON RENAL PELVIC PRESSURE IN A RAT MODEL1990 ANNUAL MEETING OF THE SECTION OF UROLOGY OF THE AMERICAN ACADEMY OF PEDIATRICSSMYTH, T. B., Shortliffe, L. M., Constantinou, C. E.WILLIAMS & WILKINS.1991: 592–96

Abstract

We describe an in vivo animal model used to study the interactions of urinary flow, and bladder pressure and fullness on renal pelvic pressure. These parameters were examined in 17 nonrefluxing Sprague-Dawley rats. At urinary flow rates less than 14 cc/kg. per hour and bladders less than 60% full, renal pelvic pressures were below 9 cm. water but at urinary flow rates more than 30 cc/kg. per hour renal pelvic pressure increased above 10 cm. water when the bladder was only 20% full. At all urinary flow rates examined renal pelvic pressure increased to more than 20 cm. water as the bladder approached 100% fullness. To quantitate the combined effects of these changes in renal pelvic pressure and urinary flow on the renal pelvis a renal pelvic work index (renal pelvic pressure times urinary flow rate) was defined. Using this index the magnitude of the change between low urinary flows with an empty bladder and high urinary flows with a full bladder can be observed. The results of these studies in this model might be applicable to high urinary flow states or bladders that fail to empty completely.

Abstract

The influence of perfusate flow rate on the two-dimensional (2-D) temperature distributions induced by hyperthermia in the canine kidney was evaluated. Localized hyperthermia was induced by ultrasound (frequency 2.040 MHz, transducer diameter 6.7 cm) in the ex-vivo perfused kidney. Temperatures were mapped using shielded copper/constantan thermocouple sensors. The 2-D temperature distribution of the kidney was obtained by pulling these sensors through a planar array of eight stainless-steel trocars inserted along its longitudinal axis. The perfusion system allowed for the control of internal/external organ temperature and type of perfusate, and it simulated vasodilation and vasoconstriction by changing the arterial volume flow rate. The temperature data obtained at flow rates ranging from 0 to 570 ml/min and power levels from 0 to 150 W showed that acoustic power densities in excess of 1.5 W/cm2 were required to maintain therapeutic temperatures in this system. Contour maps for characterizing the 2-D temperature distributions induced in this system were analysed with the introduction of a quantitative measure based on the area within a given isotherm. They show the effects of tissue heterogeneity, flow rate, and non-uniform power deposition. Time constants computed from the exponentially decaying temperatures measured following power off ranged from 5 to 555 s. These findings provide a basis for comparison with temperature measurements being acquired in the in-vivo kidney system. Information acquired from this system may facilitate the process of developing tissue-equivalent dynamic phantoms for ultrasound-induced hyperthermia. The ex-vivo model presented in this paper might be used to study the performance of alternative heating applicators, the effect of haematocrit, blood viscosity, and the use of vasoactive drugs.

Abstract

The relaxation mechanism of the antispasmodics, papaverine and thiphenamil on isolated human corpus cavernosum (CC) was investigated. CC tissues were obtained from 12 impotent men undergoing surgery for insertion of penile prostheses. CC preparations were mounted in a tissue bath and the isometric tension was recorded. Papaverine and thiphenamil consistently inhibited high-potassium ([K])-induced contractions in a dose-dependent manner. Noradrenaline (NA)-induced contractions were inhibited by both agents in a non-competitive manner. The pD'2 values were 4.77 +/- 0.20 for papaverine and 4.58 +/- 0.13 for thiphenamil. Papaverine at 10(-4) M, the concentration at which high-[K]-induced contraction was abolished, suppressed NA-induced contraction by approximately 85%. In the Ca2(+)-free solution containing two mM EGTA, NA-induced contraction was suppressed by approximately 90%. This contraction was inhibited by papaverine or thiphenamil in a dose-dependent manner and was abolished by papaverine at 10(-4). These results suggest that papaverine and thiphenamil relax CC tissue by the inhibition of extracellular Ca2+ influx (mainly voltage-dependent Ca2+ influx) and by the inhibition of release and/or storage of intracellular stored Ca2+.

Abstract

The release of endothelium-derived relaxing factor (EDRF) from human corpus cavernosum (CC) tissue was confirmed by demonstrating that bradykinin produces endothelium dependent relaxation of human CC tissue. Human CC strips were set in a tissue bath and isometric tension changes were recorded. All strips showed spontaneous contractions and produced tonic contractions by both high potassium solution and noradrenaline (NA) (10(-9) to 10(-4) M) in a dose dependent manner. In preparations precontracted with NA, relaxation was produced by bradykinin (10(-7) to 2 x 10(-6) M). Strips lacking endothelium were contracted by NA but no relaxation was observed with the addition of bradykinin. More direct evidence of the release of EDRF from human CC was demonstrated by a "sandwich" mount. We conclude that bradykinin relaxes human CC by releasing EDRF and that this EDRF may be a factor in erectile function.

Abstract

The influence of the voiding cycle and diuresis on the hydrodynamic pressures of the renal pelvis in the multicalyceal kidney of miniature pigs has been examined. Identification of the pressure patterns characteristic of the renal pelvis with an undisturbed pelviureteric and ureterovesical junction was emphasized. The frequency and amplitude of contractions in the renal pelvis were measured bilaterally. The patterns of renal pelvic pressure changes were interpreted during bladder filling and emptying and diuresis to evaluate the mechanisms facilitating the pressure isolation of the upper urinary tract. These studies were undertaken in the awake pig equipped with a long-term radiotelemetry implant transmitting renal pelvic and urinary bladder pressure. The results show that renal pelvic contractions are low-pressure events having an amplitude of 10.3 +/- 4.2 cmH2O and a frequency of 6.6 +/- 0.7 contractions/min. During basal hydration, the process of renal pelvic filling and emptying is active, with rhythmic pelvic contractions. The left and right renal pelvis demonstrate approximately equal frequency, 1.04:1.00, but are not synchronous. Furosemide-stimulated diuresis produces radical changes in the renal pelvis by transforming emptying from an active to passive mode and facilitating the transmission of voiding pressures and spontaneous bladder pressures to the kidney.

Abstract

The effects of [1-desamino-8-D-arginine]vasopressin (DDAVP) (V2 receptor agonist) and papaverine on four continuous circular smooth muscle strips in rabbit renal pelvis were studied by an isometric tension recording methods. DDAVP suppressed spontaneous contractions in a dose-dependent and region-dependent way. Papaverine suppressed these contractions in a dose-dependent way simultaneously in all four portions. These results suggest that there may be distribution differences of V2 receptors in the renal pelvis. Together with its anti-diuretic action, DDAVP may merit consideration for the treatment of renal colic.

Abstract

The frequency components of spontaneous contractility of rabbit bladder strips were examined with respect to their orientation and position. Spectra of longitudinal and transverse strips of bladder were studied in vitro in consecutively dissected segments from the same bladder. The frequency characteristics of these strips were characterized at rest and also with incremental extension to 125% of original length. Results show that transverse and longitudinal strips of bladder muscle undergo continuous spontaneous contractions in the frequency range of 0.01-0.25 Hz. The amplitude of the spontaneous contractions is not dependent on the amount of resting tension in either longitudinal or transverse strips. Longitudinal strips have a higher frequency of spontaneous variations of tension compared with the transverse strips. The amplitude of transverse strips is lowest at the base of the bladder, and the frequency components of activity increases in magnitude toward the bladder dome. Extension of transverse strips shows the generation of frequency peaks of tissues located at the middle of the bladder having a significantly lower rate of relaxation than the proximal or distal strips. Spontaneous contractility of the bladder indicates the presence of a potentially significant parameter that must be considered when tissue response to mechanical, electrical, or pharmacological stimulation is interpreted.

Abstract

An experimental study of the porcine multicalyceal pacemaker system was undertaken. In particular, the characteristic rhythmicities of in situ calyces were examined as well as rhythmicities between the calyceal system and the renal pelvis using pig kidneys perfused ex vivo via the renal artery. The temporal and spatial organization of calyceal and renal pelvic contraction rates were evaluated by simultaneously recording pressure from the renal pelvis and from three calyces. The results obtained from 15 kidneys indicate that the upper, middle, and lower calyces contract rhythmically at the essentially equal rates of 12.8 +/- 2.4, 14.0 +/- 1.6, and 13.06 +/- 2.3 min-1. The interaction between the activities of different calyces was analyzed by measuring the phase of individual calyceal contractions. Phase locking, coordination of contraction and phase oscillation, systematic fluctuations, or divergence of phase were obtained in most preparations, indicating the existance of a mechanism of coherent intercalyceal coupling. During periods in which phase locking occurred, pelvic contractions were related to all of the observed calyceal regions. When phase oscillation was present, the region of calyceal system evidencing a higher frequency was associated with pelvic contraction, whereas in the absence of calyceal coupling renal pelvic contractions could not be correlated to calyceal activity.

Abstract

Injectable materials have been used to augment the urethral sphincter and improve urinary continence with some success. However, none of these materials has received widespread use because they are difficult to inject and have been reported to migrate. We investigated the efficacy of transurethral implantation of glutaraldehyde cross-linked collagen, a highly purified bovine collagen. A total of 17 patients (16 men and 1 woman) with urinary incontinence resulting from a previous operation was selected for glutaraldehyde cross-linked collagen injection into the region of the urethral sphincter. Before and after implantation patients underwent urodynamic evaluation. Glutaraldehyde cross-linked collagen was injected into the area of the bladder neck or urinary sphincter under direct endoscopic vision. If no improvement occurred reinjection to increase the implant volume was performed at least 3 months after a previous injection. Of the 17 patients 9 were cured or improved. No complications have been reported. This investigation shows that glutaraldehyde cross-linked collagen can be injected into the urinary tract to correct urinary incontinence without observable or measurable morbidity.

Abstract

A new computerized methodology was used to acquire and analyze the relative pharmacologic sensitivity of the renal pelvis and urinary bladder of the rabbit to pharmacologic stimulation. Comparison was made of the effects of thiphenamil, verapamil and oxybutynin on the spontaneous contractions of isolated detrusor and renal pelvis. Data collected by computer were evaluated in terms of amplitude, frequency, and tension change to varying concentration of pharmacologic stimulation. Data were analyzed using a frequency/time domain algorithm developed specifically to evaluate the contribution of the oscillatory components of tension associated with smooth muscle tissues. For the renal pelvis the results show 6 X 10(-5) M thiphenamil, 10(-3) M oxybutynin, and 5 X 10(-6) M verapamil resulted in a 50% inhibition of the phasic contractions. Thiphenamil significantly increased the contractile frequency of the renal pelvis. For the bladder 10(-3) M thiphenamil resulted in a 50% inhibition of the phasic contractions, while 3 X 10(-4) M oxybutynin and 3 X 10(-6) M verapamil were needed to achieve the same level of inhibition. Thiphenamil at lower doses (10(-4) M to 5 X 10(-4) M) showed a biphasic effect--an increase of the bladder tissue activity followed by a relaxation phase--that oxybutynin and verapamil failed to produce. The results show that the calcium blocker suppresses the spontaneous activity of the upper and lower urinary tract at lower concentrations than the anticholinergic or thiphenamil.

Abstract

Urinary incontinence with detrusor instability often is refractory to pharmacological therapy as well as other conservative modalities. We report the results obtained from 10 patients with detrusor incontinence who underwent extravesical subtrigonal injection of 50 per cent ethanol. Postoperatively, 9 of the 10 patients had conversion to detrusor stability and 6 had an acontractile bladder. Of the 10 patients 9 had an excellent result for at least 10 months postoperatively with 1 patient requiring 2 additional treatments to convert to detrusor stability. Complications included fistula formation in 3 patients, requiring primary closure in 2 and ileal diversion in 1. Of the 10 patients 7 remain dry or vastly improved at a mean of 24 months of followup.

Abstract

The dynamics of pyeloureteral flow is described when there is no peristalsis and for peristalsis of high and intermediate frequencies, on the assumption that the ureter is uniform except in the mid-ureter and at the outlet. The possibility of upstream transmission of bladder pressure variations to the renal pelvis is considered. The overall behaviour depends on three principal variables, the maximum tube pressure in the contraction waves, the intrinsic peristaltic carrying capacity and the peristaltic frequency f, expressed in the form fT where T is the time for a peristaltic contraction wave to sweep through the ureter. At intermediate peristaltic frequencies (fT less than but comparable with one) oscillatory flow patterns can occur, in which periods of peristaltically driven flow alternate with extraperistaltic periods of flow through the open ureter. The kidney is better isolated from bladder pressure variations when the peristaltic frequency is high, but high peristaltic frequency can by itself lead to elevated renal pelvic pressure if the flow rate is high. Experimental observations in pigs are presented to support these conclusions.

Abstract

The cause of incontinence in a group of 11 girls (mean age 18 +/- 3 years) who had undergone internal urethrotomy during childhood was assessed. Urodynamic methods were used to characterize the detrusor, and urethral profiles were performed to identify the impact of the operation on the extrinsic and intrinsic mechanisms of urethral closure. The results show that 4 of 11 patients demonstrated detrusor instability associated with a high voiding flow rate. The average resting urethral closure pressure in all patients showed significant reduction in maximum closure pressure (62 +/- 32 cm. water) when compared to normal age-matched controls. Transmission pressures to coughing demonstrated a high percentage of transmission to the distal and mid urethra (180 +/- 20 per cent). It was concluded that the intrinsic mechanism of urethral continence as measured by the resting urethral pressure profile was compromised by the urethrotomy. However, the extrinsic mechanisms as measured by the transmission values was not affected. On the basis of these findings it is argued that internal urethrotomy compromises the closure mechanisms intrinsic to the urethra. Continence in these patients most likely is maintained by the action of extrinsic factors transmitting high closure pressures at the distal third of the urethra. Finally, it is postulated that urethrotomy patients are at increased risk for stress incontinence at an early age.

Abstract

Recordings in eight healthy female volunteers of bladder (detrusor) pressure and flow rate, obtained during bladder filling and during voiding, both through the urethra and through a catheter, demonstrate that a model of bladder function in which the detrusor muscle is considered as completely passive during filling and fully activated during voiding is inadequate. Assessment of the detrusor contraction strength by a new method (described in APPENDIX A) shows that in ideal normal voidings the contraction strength rises to values of 11-24 W/m2 and is sustained or rises slightly until the bladder is empty. During unstable detrusor contractions, which even in these healthy women are observed during bladder filling and also during inhibited voidings through the urethra, the contraction is weaker. During voidings through a catheter the detrusor contraction is weak, variable, and fades away before the bladder is empty. An elementary feedback analysis demonstrates that the effect of the micturition reflex governing detrusor behavior differs according to whether or not voiding is taking place. The reflex does not lead to a simple on-off mechanism but to a more complex behavior that is consistent with the observations and that appears to be important for the understanding of pathological obstructed micturition.

Abstract

The bladder pressure necessary to cause vesicoureteral reflux (VUR) was measured in 16 female rats. Under general anesthesia, the ureters were exposed via an abdominal incision and a pressure catheter was placed near the ureterovesical junction. Values of bladder distension and bladder pressure increase to cause VUR were obtained by injecting isotonic saline in one ureter until VUR in the opposite ureter was detected as a sudden pressure increase. After 5 min the same procedure was done on the contralateral side. This procedure was repeated eight times in each rat with a 15-min intermission. The bladder pressure at which VUR occurred was measured through a ureteral catheter. Two groups were studied: G1, control, and G2, administration of intravenous metoclopramide (0.007 mg/100 g body weight) four times.

RESTING AND STRESS URETHRAL PRESSURES AS A CLINICAL GUIDE TO THE MECHANISM OF CONTINENCE IN THE FEMALE PATIENTUROLOGIC CLINICS OF NORTH AMERICAConstantinou, C. E.1985; 12 (2): 247-258

Abstract

Urethral closure pressures are examined with respect to continence and aging. An attempt is made to interpret the inherent orientation sensitivity of microtip transducer profilometry. The transmission of cough pressures along the length of the urethra is also examined, showing that incontinence is associated with low transmission.

Abstract

We characterized the isometric pressures generated by the bladder during voluntary detrusor contraction and interruption of flow. Urodynamic studies were done in 34 healthy female volunteers, with a mean age of 29.6 plus or minus 9.3 years. Control urodynamics were done first to characterize bladder and urethral parameters to filling and voiding. Subsequently, isometric detrusor pressures were elicited during bladder filling at increments of 100 ml. by asking subjects to attempt to void against a urethral obstruction produced by an inflated Foley balloon. Isometric pressures also were obtained by interruption of flow through the lumen of the 22F Foley catheter. The results showed that the maximum isometric pressure increase generated remained relatively constant during bladder filling at 39.6 plus or minus 13.1 cm. water. This pressure is not significantly different from voiding pressures developed with a 10F urethral catheter. On the other hand, isometric pressure increases during voiding showed that the increase in bladder pressure following interruption of flow was volume sensitive. The possibility that this volume dependency may result in errors in the interpretation of bladder contractility is discussed.

Abstract

We localized the temporal and spatial distribution of pressures in the urethra to identify their contribution to continence. With the data obtained we resolved the timing between the passively transmitted and actively generated urethral pressures. Data were obtained from 11 healthy female volunteers, with a mean age of 22 years. Simultaneous measurements of bladder and urethral pressures were taken from subjects during the Valsalva maneuver and coughing, and then holding with the subject in the supine, standing and sitting positions. The ratio of urethral to bladder pressure increase and the latency between these pressure increases were analyzed. A biphasic pressure distribution results from coughing with subjects in all positions. The first phase occurs at the normalized distance of 10 to 15 per cent from the bladder neck, where the ratio of urethral to bladder pressure increase is 0.8. The second phase occurs at 60 to 70 per cent of the urethral length and has a 1.5 to 1.7 ratio of urethral to bladder pressure increase, indicating the presence of pressure magnification. Simultaneous latency measurements indicate that the pressure increase in the urethra precedes that of the bladder by 240 plus or minus 30 msec. in the region that exhibits maximum pressure magnification. These results indicate that a fast-acting contraction occurs in the distal third of the urethra, which contributes reflexly to the compressive forces of the proximal urethra, thereby preventing urine loss during stress.

Abstract

We present the results of a study designed to characterise urine transport in the healthy and chronically obstructed upper urinary tract. Fifteen healthy and 11 hydronephrotic pigs were used; experimental hydronephrosis was produced by partially obstructing the ureter. Data consisting of the peristaltic rate, bolus volume, and the urine flow rate were collected and related to varying increments of diuresis. The transmission characteristics of renal pelvic to ureteric contractions were studied by extracellular electrodes. Similarly, in hydronephrotic preparations we studied the transmission between the proximal and middle pelvis to the ureter. In healthy preparations, the contraction frequency of the renal pelvis and the ureter is identical, while in obstructive cases, the contraction frequency of the upper pelvis is not coordinated with the lower pelvis or ureter. While diuresis increased bolus volume to a maximum of 1,200% in the healthy and 660% in the hydronephrotic kidney, the peristaltic rate changed by only 45% and 50% respectively. The results of this study show that chronic ureteric obstruction alters the coordination of ureteric peristalsis and thereby disrupts the pacemaker mechanisms of the renal pelvis.

Abstract

The gradient of cellular [Na+] on [K+] ion within the renal pelvis of the rabbit was correlated with the autorhythmicity of the proximal, middle, distal and ureteropelvic regions of this structure. The results show that the maximum frequency of spontaneous pacemaker contractions occur at the proximal pelvis with a mean frequency of 4.97 +/- 0.85 contractions/min, a mean [Na+] of 91.0 +/- 33.3 mEq/kg net weight, a mean [K+] of 18.9 +/- 6.0 mEq/kg net weight. The frequency of spontaneous activity from the middle pelvis and distal pelvis decreases to mean values of 2.76 +/- 0.60 and 1.82 +/- 0.56 contractions/min. The corresponding values for [Na+] and [K+] are 78.0 +/- 27.7 and 11.8 +/- 4.7 for the middle pelvis and 66.6 +/- 32.7 and 9.75 +/- 3.4 for the distal pelvis, respectively. Normalized regression curves indicate a [Na+]gradient variation of delta [Na+] = 67.1 +/- 0.07 delta F and a [K+] gradient of delta [K+] = 39.8 - 0.06 delta F + 0.01 delta F2. Spatially, the variation of [Na+] and [K+] with distance. D, within the pelvis is given by [Na+] = 119 - 14D + D2 and [K+] = 26 - 11D + 2D2. It is concluded from this study that there is a frequency gradient between proximal renal pelvis and ureteropelvic junction which is significantly interdependent upon the cellular [Na+] on [K+] concentration gradient.

Abstract

The [Ca++] gradient within the rabbit renal pelvis was compared to its inherent pacemaker frequency. The pelvis was removed from the rabbit, sectioned, and [Ca++] ions assayed using wet ash techniques and atomic absorption spectrophotometry. Contraction frequency was measured isometrically in vitro. In the bisected pelvis it was found that both [Cu++] levels and contraction frequency were highest in the proximal section, 9.02 +/- 4.62 mEq/kg, and lower in the distal section, 6.59 +/- 2.43 mEq/kg wet weight. The mean frequency of contraction decreased from 3.69 +/- 0.81 to 2.41 +/- 0.49 min-1 in the proximal and distal regions, respectively.

Abstract

The transport of urine in the upper urinary tract of the multicalyceal kidney was studied in healthy and chronically obstructed pigs in terms of renal pelvic pressure, rate of and coordination of ureteral contractions, and bolus volume. The variations of these parameters to diuresis was examined by incremental elevation of urine output effected by intravenous infusion of mannitol. In 16 healthy animals the mean variation in urine flow was 0.01-3.20 ml/min, the change in peristaltic rate ranged from 0.763 to 5.125 min-1, and bolus volume from 0.003 to 2.083 ml.. In 14 chronically obstructed kidneys, for a mean variation in urine flow of 0.006-5.4 ml/min, peristaltic rate ranged from 0.237 to 6.095 min-1 and bolus volume from 0.00 to 1.80 ml. Discoordinated contractions, bursts of peristalsis, and incompletely transmitted pelvic contractions were characteristic of a chronically obstructed system. These observations are compared with the unobstructed unicalyceal and multicalyceal kidney. The disrupting impact of chronic ureteral obstruction on the hierarchical organization of the pyeloureteral pacemaker system is discussed.

Abstract

The characteristics of spontaneous contractility in the renal pelvis were examined in the unicalyceal kidney of the rabbit. In vitro isometric studies were done on whole as well as renal pelvic segments dissected longitudinally and radially. The results show that the contractile frequency of isolated segments was highest in the proximal region (4.188 +/- 0.162 min-1) and decreased distally to (2.178 +/- 0.330 min-1). There was no significant frequency gradient in the circumferential direction. A modulation of wave form (waxing and waning phenomena) was observed in both the proximal and middle regions of the pelvis. Based on these results, a simulation of the renal pelvic activity was made by using a chain of coupled linear oscillators. At high values of coupling a pacemaker contraction of the renal pelvis was reproduced by the coupled oscillator model. The modulation of wave form was observed when the coupling of the circumferential direction was weak. These results are discussed in the context of the hierarchically organized multiple-coupled pacemaker system, which characterizes an integrative activity of the unicalyceal renal pelvis.

Abstract

Acetylcholine failed to change the frequency of spontaneous contractions in the proximal region of isolated rabbit renal pelvis, but significantly increased the contractile frequency in the middle and distal regions, which then reached similar levels to those of the proximal region. Pretreatment with reserpine caused a decrease in the frequency of spontaneous contractions in the proximal, but not in the middle or distal regions. Reserpine-pretreated tissues developed hypersensitivity to catecholamines, while acetylcholine produced effects similar to those observed in control preparations. Atropine and N-methyl-scopolamine antagonized the action of acetylcholine in both the middle and the distal regions, suggesting that the action was exerted through muscarinic receptors. Adrenaline and alpha-stimulating drugs, but not isoprenaline, significantly increased the contractile frequency of all three tissues: the increase in the proximal region reached levels in excess of its fundamental maximal frequency. Phentolamine caused a significant decrease in the frequency of the proximal region and fully inhibited the stimulating action of catecholamines, indicating that this stimulation was mediated by alpha-adrenoceptors. The myogenic nature of pacemaking cells was confirmed by the effect of tetrodotoxin, ouabain and verapamil. The decrease in frequency in the pacemaker region of the proximal pelvis whether caused by reserpine or phentolamine indicates a significant role of catecholamines in modulating pacemaker activity.

Abstract

The transmission of intra-abdominal pressures to the urethra of the healthy female is examined with respect to cough, Valsalva and holding stimuli. A new method of recording urethral pressures using a four-channel, perfused gap catheter specifically constructed for this investigation is used. The results show that the increase of urethral pressure to stimuli is magnified at the distal urethra to a significant degree. This magnification is significantly higher than that expected by direct intra-abdominal transmission. Anatomically, the focus of urethral magnification of pressures is located 2-3 mm distal to the external urethral sphincter. The data provided from this study indicate that the mechanism of action of urethral closure to stress is active and does not directly correspond to the transmission properties of the lower urinary tract to stresses. Evidence supporting this mechanism is drawn also from the differential behavior of the proximal and distal regions of the urethra to the initiation and cessation of voiding.

Abstract

There are regional variations of the amplitude, frequency and waveform of spontaneous contractions within the isolated renal pelvis and calyx of the multicalyceal pyeloureter of the pig. The contractility of these structures was studied in normal and hydronephrotic preparations. Tissues were obtained from normal and chronically obstructed animals. In 20 normal preparations, the contractile frequency of the renal pelvis was 4.9 +/- 2.1 contractions/min, while that of the calyx was 9.5 +/- 2.2 (mean +/- SD). The recorded amplitude was 0.95 +/- 0.92 and 0.45 +/- 0.61 g, respectively. The waveform of the calyceal contractility approximated the sinusoid demonstrating a slow rise and fall in tension, while the waveform of renal pelvic smooth muscle demonstrated a faster increase in tension. Obstruction and hydronephrosis produced a minimal alteration in the frequency and amplitude of the calyceal structures, 9.1 +/- 2.2 contractions/min and 0.71 +/- 0.49 g, respectively. Hydronephrotic renal pelves demonstrated a significant increase in the frequency of spontaneous contractility 8.0 +/- 4.2 contractions/min with no change in the mean amplitude of contraction 0.88 +/- 0.90 g. These data suggest that obstruction alters the frequency of isolated renal pelvic contraction so that they approximate the frequency of isolated calyceal contractions.

Abstract

An optical detection method, using video imaging, is used to quantitatively record the frequency and velocity profile of the renal pelvis of the rabbit. It is demonstrated that concentric waves originating at the periphery of the pelvis have an initial velocity of 3.2 cm/sec, accelerating toward the pelviureteral junction reaching a final velocity of 6.4 cm/sec.

Abstract

The response of the healthy pyeloureteral system of the pig to stepwise increments of urine flow was measured using a flow-velocity, diameter probe. The following urodynamic parameters were measured: renal pelvic pressure, ureteral flow-velocity and diameter, and associated bolus volume in the range of urine flow rates of 0.3 to 10 ml per min. The results show that the diameter sensoring portion of this probe can reliably sense ureteral peristalsis over the entire range of urine flow rates; small alterations in ureteral diameter occurring in dilated ureters after high diuretic loads can also be detected. Data obtained using the flow-velocity portion of this probe indicate that at urine flow rates less than 0.5 ml per min flow-velocity changes of a bolus can be reliably identified. At these flow rates the maximum flow-velocity occurs at the leading edge of the bolus and is invariant with the size of the bolus. At urine flow rates more than 1 ml per min the flow-velocity curve is polyphasic, indicative of an alteration in the mechanism of urine transport by the ureter at these flows. Collectively, data obtained using this probe provide dynamic information concerning the physiologic properties of the upper urinary tract not currently attainable in existing pressure/flow methodologies.

Abstract

The patterns of mechanical contractility in the pyeloureteral pacemaker system were explored in an effort to identify some of the properties of initiating ureteral peristalsis. Rabbit renal pelvises were studied in vivo, in vitro perfused with Krebs solution through the renal artery and in segments. The results show that all segments of renal pelvic smooth muscle are capable of spontaneous contractions, the fornix having the highest frequency with respect to the pelvis. It is also demonstrated that the pelvic contractile wave concentrically accelerates along the renal pelvic perimeter. Under steady state conditions, renal pelvic pressure undergoes a low frequency oscillation having a period of 1--2 min which is flow-rate dependent. The results are discussed within the context of the pyeloureteral pacemaker system and the possible existence of a feedback mechanisms between the renal pelvis and the perfusion of the kidney.

Abstract

The pacemaker properties of the various regions of isolated segments of the rabbit renal pelvis were examined. The results show that pacemaker frequency and waveform of contraction change significantly within the renal pelvis. The highest frequency was encountered at the fornix, while the ureteropelvic junction is lowest.

Abstract

Temporal and distributive properties of ureteral peristaltic contractions in the anesthetized pig have been examined. Interperistaltic time intervals have been recorded, and their frequency during different urine flow rates has been compared. The results show that ureteral peristalsis is increased at high urine flow rates to a maximum of approximately 0.06 Hz. It is further shown from the interperistaltic histograms that ureteral contractions are not clustered into a discreet multimodal spectrum. This represents the first evidence that the multicalyceal kidney has a system of pacemakers of differing fundamental frequencies, tending toward synchronism as urine flow increases.

Abstract

The continuity of ureteral peristaltic conduction along the ureter of the dog is examined using two pairs of extracellular macroelectrodes. At urine flow rates below 3 ml/min, ureteral contractions initiated by the pacemaker are propagated without interruption along the entire length of the ureter, and at sustained diuretic levels greater than 3-5 ml/min, ectopic peristaltic and retrograde events may be initiated along the length of the ureter. Also, continued maintenance of diuresis results in decremental conduction along the upper third of the ureter with the ultimate possiblity of pacemaker failure.

Abstract

The control of ureteral peristaltic contractions by a pacemaker system is shown in a series of experimental observations on the anesthetized dog. Data are presented to illustrate the influence of pacemaker frequency on ureteral rate and bolus volume during oliguria and transient diuresis. Pacemaker frequency was determined from the pressure wave form of the renal pelvis and peristaltic rate was measured electrophysiologically. The bolus volume associated with each peristaltic contraction was recorded by a drop counter and correlated with pacemaker and ureteral activity. The results show that the pacemaker frequency remains constant over urine flow rates in the range of 0.3 to 15 ml per min. It is also shown that the pacemaker frequency is constant during transient increases in flow rate of more than one order of magnitude. During diuresis, the peristaltic rate changes in quantum steps determined by the fundamental frequency of the pacemaker, and at flow rates greater than 2 ml per min the ureter contracts at the pacemaker rate. Further increases in flow are accommodated by increasing the amount of urine transported by each bolus. The urologic importance of these observations on pacemaker function is discussed in terms of the unicalyceal and multicalyceal upper urinary tract.

Abstract

The influence of Pentothal anesthesia in blocking the mechanism intimating ureteral peristalsis in the dog is examined. Pressure measurements of pacemaker rhythmicity were made through renal cortical catheterization of the renal pelvis. Simultaneously, ureteral recordings were made by extracellular electromyography of the ureteral smooth muscle wall. It is shown that Pentothal anesthesia transiently blocks the spontaneous and rhythmic contractions of the renal pelvis and inhibits the generation of ureteral peristaltic contractions. It is demonstrated that repeated or prolonged pacemaker blockade results in an open ureteropelvic junction and aperistalsis. A discussion of the possible implication of these observations is given.

Abstract

Ureteral contractions occur at intervals which are integral multiples of the period of pacemaker potentials recorded in vitro from the renal pelvis with a sucrose gap, suggesting that a gating mechanism in the pyeloureter regulates the rate at which the pacemaker initiates contractions.

STATISTICAL PROPERTIES OF TEMPORAL AND SPATIAL-DISTRIBUTION OF INTERPERISTALTIC INTERVALS AND THEIR RELATIONSHIP TO PACEMAKER AND RESPIRATORY RHYTHMICITYUROLOGIA INTERNATIONALISConstantinou, C. E.1975; 30 (5): 369-380

Abstract

A straightforward method is outlined for the presentation of the temporal and spatial characteristics of interperistaltic intervals obtained from the canine ureter. The fundamental statistical property of ureteral peristaltic contractions is demonstrated to be multimodal. This is characterized by a basic rate and whole number multiples of that rate. The methods for identifying the relationship of peristalsis with the pacemaker and respiratory rate is outlined.